Coronaviruses

A topical collection in Viruses (ISSN 1999-4915). This collection belongs to the section "Coronaviruses".

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Editors


E-Mail Website
Collection Editor
1. Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14625, USA
2. Texas Biomedical Research Institute, San Antonio, TX 78245, USA
Interests: virology; vaccines; antivirals; influenza viruses; arenaviruses; Zika virus; coronavirus; SARS-CoV-2; COVID-19; innate immunity; adaptive immunity; interferon; virus-host interactions
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Collection Editor
Department of Molecular and Cell Biology, National Center for Biotechnology, Darwin 3, 28049 Madrid, Spain
Interests: virology; virus-host interaction; coronavirus; vaccines; antivirals; flavivirus; Zika virus
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Human coronaviruses (HCoVs), including NL63, 229E, OC43, and HKU1, are enveloped, single-stranded, positive-sense RNA viruses responsible for seasonal mild and moderate respiratory illness (229E and OC43) and, in some cases, bronchiolitis and pneumonia (NL63 and HKU1). However, two HCoVs (SARS and MERS) have been shown to cause severe morbidity and mortality in humans. Recently (December 2019), a novel HCoV, severe acute respiratory syndrome CoV-2 (SARS-CoV-2), was identified in the city of Wuhan in China, and has been responsible for the COVID-19 pandemic, with an alarming case fatality rate, posing an unprecedented threat to human health and the economy. To date, three vaccines have been approved by the Food and Drug Administration (FDA) for emergency use. However, efforts to develop effective countermeasures to deal with SARS-CoV-2 and other HCoV infections are an urgent need.

In this Topical Collection about HCoVs, we aim to cover all the aspects related to coronavirus disease not related to SARS-CoV-2 infection and/or COVID-19, including virus–host interactions, viral infection, transmission, pathogenesis, animal models, antivirals, vaccine development, neutralizing antibodies, immunity, innate and adaptive immune responses, prophylactics, therapeutics, and reverse genetics.

We hope that the collection of research articles in this Topical Collection will provide researchers with a better understanding of HCoV infections, with the final goal of using this information for the development of prophylactic and/or therapeutic approaches to controlling these important human respiratory pathogens.

Prof. Dr. Luis Martinez-Sobrido
Dr. Fernando Almazan Toral
Collection Editors

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Keywords

  • coronavirus
  • HCoV-OC43
  • HCoV-229E
  • HCoV-NL63
  • HCoV-HKU1
  • SARS-CoV
  • MERS-CoV
  • reverse genetics
  • immunity
  • innate immunity
  • adaptive immunity
  • virus-host interactions
  • antivirals/therapeutics
  • vaccines/prophylactics
  • inactivated vaccines
  • live-attenuated vaccines
  • reporter viruses
  • animal models

Related Special Issues

Published Papers (97 papers)

2024

Jump to: 2023, 2022, 2021, 2020

15 pages, 3549 KiB  
Article
Transcriptomic Analysis of PDCoV-Infected HIEC-6 Cells and Enrichment Pathways PI3K-Akt and P38 MAPK
by Yuhang Jiang, Guoqing Zhang, Letian Li, Maopeng Wang, Jing Chen, Pengfei Hao, Zihan Gao, Jiayi Hao, Chang Li and Ningyi Jin
Viruses 2024, 16(4), 579; https://doi.org/10.3390/v16040579 - 9 Apr 2024
Viewed by 622
Abstract
Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) [...] Read more.
Porcine Deltacoronavirus (PDCoV) is a newly identified coronavirus that causes severe intestinal lesions in piglets. However, the understanding of how PDCoV interacts with human hosts is limited. In this study, we aimed to investigate the interactions between PDCoV and human intestinal cells (HIEC-6) by analyzing the transcriptome at different time points post-infection (12 h, 24 h, 48 h). Differential gene analysis revealed a total of 3560, 5193, and 4147 differentially expressed genes (DEGs) at 12 h, 24 h, and 48 h, respectively. The common genes among the DEGs at all three time points were enriched in biological processes related to cytokine production, extracellular matrix, and cytokine activity. KEGG pathway analysis showed enrichment of genes involved in the p53 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway. Further analysis of highly expressed genes among the DEGs identified significant changes in the expression levels of BUB1, DDIT4, ATF3, GBP2, and IRF1. Comparison of transcriptome data at 24 h with other time points revealed 298 DEGs out of a total of 6276 genes. KEGG analysis of these DEGs showed significant enrichment of pathways related to viral infection, specifically the PI3K-Akt and P38 MAPK pathways. Furthermore, the genes EFNA1 and KITLG, which are associated with viral infection, were found in both enriched pathways, suggesting their potential as therapeutic or preventive targets for PDCoV infection. The enhancement of PDCoV infection in HIEC-6 was observed upon inhibition of the PI3K-Akt and P38 MAPK signaling pathways using sophoridine. Overall, these findings contribute to our understanding of the molecular mechanisms underlying PDCoV infection in HIEC-6 cells and provide insights for developing preventive and therapeutic strategies against PDCoV infection. Full article
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20 pages, 2284 KiB  
Article
Acellular Human Amniotic Fluid-Derived Extracellular Vesicles as Novel Anti-Inflammatory Therapeutics against SARS-CoV-2 Infection
by Debarati Chanda, Tania Del Rivero, Roshan Ghimire, Sunil More, Maria Ines Mitrani, Michael A. Bellio and Rudragouda Channappanavar
Viruses 2024, 16(2), 273; https://doi.org/10.3390/v16020273 - 9 Feb 2024
Viewed by 1262
Abstract
The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. [...] Read more.
The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19. Full article
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15 pages, 3123 KiB  
Article
Sulfated Glycans Inhibit the Interaction of MERS-CoV Receptor Binding Domain with Heparin
by Jiyuan Yang, Yuefan Song, Weihua Jin, Ke Xia, Grace C. Burnett, Wanjin Qiao, John T. Bates, Vitor H. Pomin, Chunyu Wang, Mingqiang Qiao, Robert J. Linhardt, Jonathan S. Dordick and Fuming Zhang
Viruses 2024, 16(2), 237; https://doi.org/10.3390/v16020237 - 2 Feb 2024
Cited by 1 | Viewed by 1007
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of [...] Read more.
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents. Full article
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2023

Jump to: 2024, 2022, 2021, 2020

12 pages, 3838 KiB  
Article
Virological Characteristics of Five SARS-CoV-2 Variants, Including Beta, Delta and Omicron BA.1, BA.2, BA.5
by Yan Zeng, Fei Xia, Changfu Guo, Chunxia Hu, Yuwei Li, Xiang Wang, Qin Wu, Zhuo Chen, Jia Lu and Zejun Wang
Viruses 2023, 15(12), 2394; https://doi.org/10.3390/v15122394 - 8 Dec 2023
Viewed by 949
Abstract
SARS-CoV-2 variants of concern (VOCs) show increasing transmissibility and infectivity and induce substantial injuries to human health and the ecology. Therefore, it is vital to understand the related features for controlling infection. In this study, SARS-CoV-2 WIV04 (prototype) and five VOCs (Beta, Delta, [...] Read more.
SARS-CoV-2 variants of concern (VOCs) show increasing transmissibility and infectivity and induce substantial injuries to human health and the ecology. Therefore, it is vital to understand the related features for controlling infection. In this study, SARS-CoV-2 WIV04 (prototype) and five VOCs (Beta, Delta, Omicron BA.1, BA.2 and BA.5 variants) were inoculated in Vero cells to observe their growth activities. Apart from evaluating the environmental stability at different temperatures, residual virus titers and infectivity at different temperatures (4 °C, room temperature (RT) and 37 °C) were measured over 7 days. The experiment also assessed the infectivity for different incubation durations. The growth capacity assay suggested that the WIV04, Beta and Delta variants replicated efficiently in Vero cells compared with Omicron Variants, and BA.2 replicated more efficiently in Vero cells than BA.1 and BA.5. In addition, all variants exhibited longer survivals at 4 °C and could remain infectious after 7 days, compared to RT’ survival after 5 days and at 37 °C after 1 day. The virus infection assay indicated that the Omicron variant had a weaker ability to infect cells compared to the WIV04, Beta and Delta strains, and a longer infection time was required for these strains, except for BA.2. Full article
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11 pages, 1036 KiB  
Article
Evaluation of SARS-CoV-2-Positive Patients with Suspected Reinfection
by Aytaj Allahverdiyeva, Ali Ağaçfidan, Lerzan Dogan, Mustafa Önel, Hayriye Kırkoyun Uysal, Alpay Medetalibeyoğlu, Naci Şenkal, Elvin Alaskarov and Sevim Meşe
Viruses 2023, 15(11), 2222; https://doi.org/10.3390/v15112222 - 7 Nov 2023
Viewed by 1232
Abstract
The aim of this study was to investigate the reinfection rates and characteristics of SARS-CoV-2 in individuals with SARS-CoV-2 RNA present in their clinical specimens for COVID-19. Our data from the COVID-19 Laboratory of Istanbul University were analyzed for 27,240 cases between 27 [...] Read more.
The aim of this study was to investigate the reinfection rates and characteristics of SARS-CoV-2 in individuals with SARS-CoV-2 RNA present in their clinical specimens for COVID-19. Our data from the COVID-19 Laboratory of Istanbul University were analyzed for 27,240 cases between 27 March 2020 to 8 February 2022. Demographic characteristics, vaccination statuses, comorbidities, and laboratory findings were evaluated in cases with suspected reinfection, as determined by the presence of SARS-CoV-2 RNA at a rate of 0.3% in clinical specimens. When comparing laboratory values, leukocyte counts were lower in the second and third infections compared with the first infection (p = 0.035), and neutrophil counts were lower in the second infection (p = 0.009). Symptoms varied, with coughing being common in the first infection and malaise being common in subsequent infections. These results suggest that it is important to continue to monitor reinfection rates and develop strategies to prevent reinfection. Our results also suggest that clinicians should be aware of the possibility of reinfection and monitor patients for recurrent symptoms. Full article
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24 pages, 4245 KiB  
Article
COVID-19 Incidence Proportion as a Function of Regional Testing Strategy, Vaccination Coverage, and Vaccine Type
by Areg A. Totolian, Viacheslav S. Smirnov, Alexei A. Krasnov, Edward S. Ramsay, Vladimir G. Dedkov and Anna Y. Popova
Viruses 2023, 15(11), 2181; https://doi.org/10.3390/v15112181 - 30 Oct 2023
Cited by 1 | Viewed by 1062
Abstract
Introduction: The COVID-19 pandemic has become a serious challenge for humanity almost everywhere globally. Despite active vaccination around the world, the incidence proportion in different countries varies significantly as of May 2022. The reason may be a combination of demographic, immunological, and epidemiological [...] Read more.
Introduction: The COVID-19 pandemic has become a serious challenge for humanity almost everywhere globally. Despite active vaccination around the world, the incidence proportion in different countries varies significantly as of May 2022. The reason may be a combination of demographic, immunological, and epidemiological factors. The purpose of this study was to analyze possible relationships between COVID-19 incidence proportion in the population and the types of SARS-CoV-2 vaccines used in different countries globally, taking into account demographic and epidemiological factors. Materials and methods: An initial database was created of demographic and immunoepidemiological information about the COVID-19 situation in 104 countries collected from published official sources and repository data. The baseline included, for each country, population size and density; SARS-CoV-2 testing coverage; vaccination coverage; incidence proportion; and a list of vaccines that were used, including their relative share among all vaccinations. Subsequently, the initial data set was stratified by population and vaccination coverage. The final data set was subjected to statistical processing both in general and taking into account population testing coverage. Results: After formation of the final data set (including 53 countries), it turned out that reported COVID-19 case numbers correlated most strongly with testing coverage and the proportions of vaccine types used, specifically, mRNA (V1); vector (V2); peptide/protein (V3); and whole-virion/inactivated (V4). Due to the fact that an inverse correlation was found between ‘reported COVID-19 case numbers’ with V2, V3, and V4, these three vaccine types were also combined into one analytic group, ‘non-mRNA group’ vaccines (Vnmg). When the relationship between vaccine type and incidence proportion was examined, minimum incidence proportion was noted at V1:Vnmg ratios (%:%) from 0:100 to 30:70. Maximum incidence proportion was seen with V1:Vnmg from 80:20 to 100:0. On the other hand, we have shown that the number of reported COVID-19 cases in different countries largely depends on testing coverage. To offset this factor, countries with low and extremely high levels of testing were excluded from the data set; it was then confirmed that the largest number of reported COVID-19 cases occurred in countries with a dominance of V1 vaccines. The fewest reported cases were seen in countries with a dominance of Vnmg vaccines. Conclusion: In this paper, we have shown for the first time that the level of reported COVID-19 incidence proportion depends not only on SARS-CoV-2 testing and vaccination coverage, which is quite logical, but probably also on the vaccine types used. With the same vaccination level and testing coverage, those countries that predominantly use vector and whole-virion vaccines feature incidence proportion that is significantly lower than countries that predominantly use mRNA vaccines. Full article
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21 pages, 4851 KiB  
Article
The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry
by Xiao Yuan, Xiaoman Zhang, Huan Wang, Xiang Mao, Yingjie Sun, Lei Tan, Cuiping Song, Xusheng Qiu, Chan Ding and Ying Liao
Viruses 2023, 15(10), 2001; https://doi.org/10.3390/v15102001 - 26 Sep 2023
Viewed by 1359
Abstract
Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the [...] Read more.
Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the IBV and PEDV life cycles was investigated. When the UPS was suppressed by pharmacological inhibition at the early infection stage, IBV and PEDV infectivity were severely impaired. Further study showed that inhibition of UPS did not change the internalization of virus particles; however, by using R18 and DiOC-labeled virus particles, we found that inhibition of UPS prevented the IBV and PEDV membrane fusion with late endosomes or lysosomes. In addition, proteasome inhibitors blocked the degradation of the incoming viral protein N, suggesting the uncoating process and genomic RNA release were suppressed. Subsequently, the initial translation of genomic RNA was blocked. Thus, UPS may target the virus-cellular membrane fusion to facilitate the release of incoming viruses from late endosomes or lysosomes, subsequently blocking the following virus uncoating, initial translation, and replication events. Similar to the observation of proteasome inhibitors, ubiquitin-activating enzyme E1 inhibitor PYR-41 also impaired the entry of IBV, enhanced the accumulation of ubiquitinated proteins, and depleted mono-ubiquitin. In all, this study reveals an important role of UPS in coronavirus entry by preventing membrane fusion and identifies UPS as a potential target for developing antiviral therapies for coronavirus. Full article
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8 pages, 1116 KiB  
Communication
Dynamic Evolution of SARS-CoV-2 in a Patient on Chemotherapy
by Weihua Huang, Changhong Yin, Kimberly P. Briley, William A. B. Dalzell and John T. Fallon
Viruses 2023, 15(8), 1759; https://doi.org/10.3390/v15081759 - 18 Aug 2023
Viewed by 1347
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved significantly during the pandemic and resulted in daunting numbers of genomic sequences. Tracking SARS-CoV-2 evolution during persistent cases could provide insight into the origins and dynamics of new variants. We report here a case [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved significantly during the pandemic and resulted in daunting numbers of genomic sequences. Tracking SARS-CoV-2 evolution during persistent cases could provide insight into the origins and dynamics of new variants. We report here a case of B-cell acute lymphocytic leukemia on chemotherapy with infection of SARS-CoV-2 for more than two months. Genomic surveillance of his serial SARS-CoV-2-positive specimens revealed two unprecedented large deletions, Δ15–26 and Δ138–145, in the viral spike protein N-terminal domain (NTD) and demonstrated their dynamic shifts in generating these new variants. Located at antigenic supersites, these large deletions are anticipated to dramatically change the spike protein NTD in three-dimensional protein structure prediction, which may lead to immune escape but reduce their viral transmissibility. In summary, we present here a new viral evolutionary trajectory in a patient on chemotherapy. Full article
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17 pages, 2772 KiB  
Article
Mutation Analysis of SARS-CoV-2 Variants Isolated from Symptomatic Cases from Andhra Pradesh, India
by Mudhigeti Nagaraja, Kodavala Sireesha, Anagoni Srikar, Katari Sudheer Kumar, Alladi Mohan, Bhuma Vengamma, Chejarla Tirumala, Anju Verma and Usha Kalawat
Viruses 2023, 15(8), 1656; https://doi.org/10.3390/v15081656 - 29 Jul 2023
Cited by 1 | Viewed by 1273
Abstract
There has been a continuous evolution in the SARS-CoV-2 genome; therefore, it is necessary to monitor the shifts in the SARS-CoV-2 variants. This study aimed to detect various SARS-CoV-2 variants circulating in the state of Andhra Pradesh, India. The study attempted to sequence [...] Read more.
There has been a continuous evolution in the SARS-CoV-2 genome; therefore, it is necessary to monitor the shifts in the SARS-CoV-2 variants. This study aimed to detect various SARS-CoV-2 variants circulating in the state of Andhra Pradesh, India. The study attempted to sequence the complete S-gene of SARS-CoV-2 of 104 clinical samples using Sanger’s method to analyze and compare the mutations with the global prevalence. The method standardized in this study was able to amplify the complete length of the S-gene (3822 bp). The resulting nucleotide and amino acid mutations were analyzed and compared with the local and global SARS-CoV-2 databases using Nextclade and GISAID tools. The Delta variant was the most common variant reported in the present study, followed by the Omicron variant. A variant name was not assigned to thirteen samples using the Nextclade tool. There were sixty-nine types of amino acid substitutions reported (excluding private mutations) throughout the spike gene. The T95I mutation was observed predominantly in Delta variants (15/38), followed by Kappa (3/8) and Omicron (1/31). Nearly all Alpha and Omicron lineages had the N501Y substitution; Q493R was observed only in the Omicron lineage; and other mutations (L445, F486, and S494) were not observed in the present study. Most of these mutations found in the Omicron variant are located near the furin cleavage site, which may play a role in the virulence, pathogenicity, and transmission of the virus. Phylogenetic analysis showed that the 104 complete CDS of SARS-CoV-2 belonged to different phylogenetic clades like 20A, 20B, 20I (Alpha), 21A (Delta), 21B (Kappa), 21I (Delta), 21J (Delta), and 21L (Omicron). Full article
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16 pages, 4324 KiB  
Article
Risk Assessment of the Possible Intermediate Host Role of Pigs for Coronaviruses with a Deep Learning Predictor
by Shuyang Jiang, Sen Zhang, Xiaoping Kang, Ye Feng, Yadan Li, Maoshun Nie, Yuchang Li, Yuehong Chen, Shishun Zhao, Tao Jiang and Jing Li
Viruses 2023, 15(7), 1556; https://doi.org/10.3390/v15071556 - 15 Jul 2023
Cited by 2 | Viewed by 1159
Abstract
Swine coronaviruses (CoVs) have been found to cause infection in humans, suggesting that Suiformes might be potential intermediate hosts in CoV transmission from their natural hosts to humans. The present study aims to establish convolutional neural network (CNN) models to predict host adaptation [...] Read more.
Swine coronaviruses (CoVs) have been found to cause infection in humans, suggesting that Suiformes might be potential intermediate hosts in CoV transmission from their natural hosts to humans. The present study aims to establish convolutional neural network (CNN) models to predict host adaptation of swine CoVs. Decomposing of each ORF1ab and Spike sequence was performed with dinucleotide composition representation (DCR) and other traits. The relationship between CoVs from different adaptive hosts was analyzed by unsupervised learning, and CNN models based on DCR of ORF1ab and Spike were built to predict the host adaptation of swine CoVs. The rationality of the models was verified with phylogenetic analysis. Unsupervised learning showed that there is a multiple host adaptation of different swine CoVs. According to the adaptation prediction of CNN models, swine acute diarrhea syndrome CoV (SADS-CoV) and porcine epidemic diarrhea virus (PEDV) are adapted to Chiroptera, swine transmissible gastroenteritis virus (TGEV) is adapted to Carnivora, porcine hemagglutinating encephalomyelitis (PHEV) might be adapted to Primate, Rodent, and Lagomorpha, and porcine deltacoronavirus (PDCoV) might be adapted to Chiroptera, Artiodactyla, and Carnivora. In summary, the DCR trait has been confirmed to be representative for the CoV genome, and the DCR-based deep learning model works well to assess the adaptation of swine CoVs to other mammals. Suiformes might be intermediate hosts for human CoVs and other mammalian CoVs. The present study provides a novel approach to assess the risk of adaptation and transmission to humans and other mammals of swine CoVs. Full article
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18 pages, 2479 KiB  
Article
Generation of a SARS-CoV-2 Reverse Genetics System and Novel Human Lung Cell Lines That Exhibit High Virus-Induced Cytopathology
by Juveriya Qamar Khan, Megha Rohamare, Karthic Rajamanickam, Kalpana K. Bhanumathy, Jocelyne Lew, Anil Kumar, Darryl Falzarano, Franco J. Vizeacoumar and Joyce A. Wilson
Viruses 2023, 15(6), 1281; https://doi.org/10.3390/v15061281 - 30 May 2023
Viewed by 2013
Abstract
The global COVID-19 pandemic continues with continued cases worldwide and the emergence of new SARS-CoV-2 variants. In our study, we have developed novel tools with applications for screening antivirals, identifying virus–host dependencies, and characterizing viral variants. Using reverse genetics, we rescued SARS-CoV-2 Wuhan1 [...] Read more.
The global COVID-19 pandemic continues with continued cases worldwide and the emergence of new SARS-CoV-2 variants. In our study, we have developed novel tools with applications for screening antivirals, identifying virus–host dependencies, and characterizing viral variants. Using reverse genetics, we rescued SARS-CoV-2 Wuhan1 (D614G variant) wild type (WTFL) and reporter virus (NLucFL) using molecular BAC clones. The replication kinetics, plaque morphology, and titers were comparable between viruses rescued from molecular clones and a clinical isolate (VIDO-01 strain). Furthermore, the reporter SARS-CoV-2 NLucFL virus exhibited robust luciferase values over the time course of infection and was used to develop a rapid antiviral assay using remdesivir as proof-of-principle. In addition, as a tool to study lung-relevant virus–host interactions, we established novel human lung cell lines that support SARS-CoV-2 infection with high virus-induced cytopathology. Six lung cell lines (NCI-H23, A549, NCI-H1703, NCI-H520, NCI-H226, and HCC827) and HEK293T cells were transduced to stably express ACE2 and tested for their ability to support virus infection. A549ACE2 B1 and HEK293TACE2 A2 cell lines exhibited more than 70% virus-induced cell death, and a novel lung cell line, NCI-H23ACE2 A3, showed about ~99% cell death post-infection. These cell lines are ideal for assays relying on live–dead selection, such as CRISPR knockout and activation screens. Full article
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11 pages, 2971 KiB  
Article
Porcine Deltacoronavirus-like Particles Produced by a Single Recombinant Baculovirus Elicit Virus-Specific Immune Responses in Mice
by Yangkun Liu, Xueying Han, Yaqi Qiao, Tiejun Wang and Lunguang Yao
Viruses 2023, 15(5), 1095; https://doi.org/10.3390/v15051095 - 29 Apr 2023
Cited by 1 | Viewed by 1661
Abstract
Porcine deltacoronavirus (PDCoV) causes diarrhea and vomiting in neonatal piglets worldwide and has the potential for cross-species transmission. Therefore, virus-like particles (VLPs) are promising vaccine candidates because of their safety and strong immunogenicity. To the best of our knowledge, the present study reported [...] Read more.
Porcine deltacoronavirus (PDCoV) causes diarrhea and vomiting in neonatal piglets worldwide and has the potential for cross-species transmission. Therefore, virus-like particles (VLPs) are promising vaccine candidates because of their safety and strong immunogenicity. To the best of our knowledge, the present study reported for the first time the generation of PDCoV VLPs using a baculovirus expression vector system, and electron micrograph analyses revealed that PDCoV VLPs appeared as spherical particles with a diameter similar to that of the native virions. Furthermore, PDCoV VLPs effectively induced mice to produce PDCoV-specific IgG and neutralizing antibodies. In addition, VLPs could stimulate mouse splenocytes to produce high levels of cytokines IL-4 and IFN-γ. Moreover, the combination of PDCoV VLPs and Freund’s adjuvant could improve the level of the immune response. Together, these data showed that PDCoV VLPs could effectively elicit humoral and cellular immunity in mice, laying a solid foundation for developing VLP-based vaccines to prevent PDCoV infections. Full article
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2 pages, 170 KiB  
Correction
Correction: Yu et al. Comparison of Physical and Biochemical Characterizations of SARS-CoV-2 Inactivated by Different Treatments. Viruses 2022, 14, 1938
by Shouzhi Yu, Yangyang Wei, Hongyang Liang, Wenheng Ji, Zhen Chang, Siman Xie, Yichuan Wang, Wanli Li, Yingwei Liu, Hao Wu, Jie Li, Hui Wang and Xiaoming Yang
Viruses 2023, 15(5), 1035; https://doi.org/10.3390/v15051035 - 23 Apr 2023
Viewed by 647
Abstract
In the original publication [...] Full article
11 pages, 1112 KiB  
Review
SARS-CoV-2 Reinfection and Severity of the Disease: A Systematic Review and Meta-Analysis
by Nhu Ngoc Nguyen, Y Ngoc Nguyen, Van Thuan Hoang, Matthieu Million and Philippe Gautret
Viruses 2023, 15(4), 967; https://doi.org/10.3390/v15040967 - 14 Apr 2023
Cited by 15 | Viewed by 12884
Abstract
Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, we summarize the results of 23 studies [...] Read more.
Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, we summarize the results of 23 studies addressing SARS-CoV-2 reinfections. A total of 23,231 reinfected patients were included, with pooled estimated reinfection rates ranging from 0.1 to 6.8%. Reinfections were more prevalent during the Omicron variant period. The mean age of reinfected patients was 38.0 ± 6. years and females were predominant among reinfected patients (M/F = 0.8). The most common symptoms during the first and second infection were fever (41.1%), cough (35.7% and 44.6%), myalgia (34.5% and 33.3%), fatigue (23.8% and 25.6%), and headaches (24.4% and 21.4%). No significant differences of clinical pattern were observed between primary infection and reinfection. No significant differences in the severity of infection were observed between primary infection and reinfection. Being female, being a patient with comorbidities, lacking anti-nucleocapsid IgG after the first infection, being infected during the Delta and Omicron wave, and being unvaccinated were associated with a higher risk of reinfection. Conflicting age-related findings were found in two studies. Reinfection with SARS-CoV-2 suggests that natural immunity is not long-lasting in COVID-19 patients. Full article
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10 pages, 855 KiB  
Article
Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting
by Yoshikazu Mutoh, Takumi Umemura, Takeshi Nishikawa, Kaho Kondo, Yuta Nishina, Kazuaki Soejima, Yoichiro Noguchi, Tomohiro Bando, Sho Ota, Tatsuki Shimahara, Shuko Hirota, Satoshi Hagimoto, Reoto Takei, Jun Fukihara, Hajime Sasano, Yasuhiko Yamano, Toshiki Yokoyama, Kensuke Kataoka, Toshiaki Matsuda, Tomoki Kimura, Toshihiko Ichihara and Yasuhiro Kondohadd Show full author list remove Hide full author list
Viruses 2023, 15(3), 811; https://doi.org/10.3390/v15030811 - 22 Mar 2023
Cited by 9 | Viewed by 3102
Abstract
Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared [...] Read more.
Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low. Full article
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18 pages, 7178 KiB  
Article
Evaluation of SARS-CoV-2 ORF7a Deletions from COVID-19-Positive Individuals and Its Impact on Virus Spread in Cell Culture
by Maria Clara da Costa Simas, Sara Mesquita Costa, Priscila da Silva Figueiredo Celestino Gomes, Nádia Vaez Gonçalves da Cruz, Isadora Alonso Corrêa, Marcos Romário Matos de Souza, Marcos Dornelas-Ribeiro, Tatiana Lucia Santos Nogueira, Caleb Guedes Miranda dos Santos, Luísa Hoffmann, Amilcar Tanuri, Rodrigo Soares de Moura-Neto, Clarissa R. Damaso, Luciana Jesus da Costa and Rosane Silva
Viruses 2023, 15(3), 801; https://doi.org/10.3390/v15030801 - 21 Mar 2023
Cited by 3 | Viewed by 2537
Abstract
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the COVID-19 outbreak, posed a primary concern of public health worldwide. The most common changes in SARS-CoV-2 are single nucleotide substitutions, also reported insertions and deletions. This work investigates the presence of [...] Read more.
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the COVID-19 outbreak, posed a primary concern of public health worldwide. The most common changes in SARS-CoV-2 are single nucleotide substitutions, also reported insertions and deletions. This work investigates the presence of SARS-CoV-2 ORF7a deletions identified in COVID-19-positive individuals. Sequencing of SARS-CoV-2 complete genomes showed three different ORF7a size deletions (190-nt, 339-nt and 365-nt). Deletions were confirmed through Sanger sequencing. The ORF7a∆190 was detected in a group of five relatives with mild symptoms of COVID-19, and the ORF7a∆339 and ORF7a∆365 in a couple of co-workers. These deletions did not affect subgenomic RNAs (sgRNA) production downstream of ORF7a. Still, fragments associated with sgRNA of genes upstream of ORF7a showed a decrease in size when corresponding to samples with deletions. In silico analysis suggests that the deletions impair protein proper function; however, isolated viruses with partial deletion of ORF7a can replicate in culture cells similarly to wild-type viruses at 24 hpi, but with less infectious particles after 48 hpi. These findings on deleted ORF7a accessory protein gene, contribute to understanding SARS-CoV-2 phenotypes such as replication, immune evasion and evolutionary fitness as well insights into the role of SARS-CoV-2_ORF7a in the mechanism of virus-host interactions. Full article
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10 pages, 4741 KiB  
Article
Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses
by Sarah N. Zvornicanin, Ala M. Shaqra, Qiuyu J. Huang, Elizabeth Ornelas, Mallika Moghe, Mark Knapp, Stephanie Moquin, Dustin Dovala, Celia A. Schiffer and Nese Kurt Yilmaz
Viruses 2023, 15(3), 781; https://doi.org/10.3390/v15030781 - 18 Mar 2023
Cited by 1 | Viewed by 1989
Abstract
With the spread of SARS-CoV-2 throughout the globe causing the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization and inhibitor design mostly focused on [...] Read more.
With the spread of SARS-CoV-2 throughout the globe causing the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization and inhibitor design mostly focused on these two genera. However, viruses from the delta and gamma genera also infect mammals and pose a potential zoonotic transmission threat. Here, we determined the inhibitor-bound crystal structures of the main protease (Mpro) from the delta-CoV porcine HKU15 and gamma-CoV SW1 from the beluga whale. A comparison with the apo structure of SW1 Mpro, which is also presented here, enabled the identification of structural arrangements upon inhibitor binding at the active site. The cocrystal structures reveal binding modes and interactions of two covalent inhibitors, PF-00835231 (active form of lufotrelvir) bound to HKU15, and GC376 bound to SW1 Mpro. These structures may be leveraged to target diverse coronaviruses and toward the structure-based design of pan-CoV inhibitors. Full article
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14 pages, 1791 KiB  
Article
Effects of SARS-CoV-2 Omicron BA.1 Spike Mutations on T-Cell Epitopes in Mice
by Yudong Wang, Busen Wang, Zhenghao Zhao, Jinghan Xu, Zhe Zhang, Jinlong Zhang, Yi Chen, Xiaohong Song, Wanru Zheng, Lihua Hou, Shipo Wu and Wei Chen
Viruses 2023, 15(3), 763; https://doi.org/10.3390/v15030763 - 16 Mar 2023
Cited by 5 | Viewed by 1829
Abstract
T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike [...] Read more.
T-cell immunity plays an important role in the control of SARS-CoV-2 and has a great cross-protective effect on the variants. The Omicron BA.1 variant contains more than 30 mutations in the spike and severely evades humoral immunity. To understand how Omicron BA.1 spike mutations affect cellular immunity, the T-cell epitopes of SARS-CoV-2 wild-type and Omicron BA.1 spike in BALB/c (H-2d) and C57BL/6 mice (H-2b) were mapped through IFNγ ELISpot and intracellular cytokine staining assays. The epitopes were identified and verified in splenocytes from mice vaccinated with the adenovirus type 5 vector encoding the homologous spike, and the positive peptides involved in spike mutations were tested against wide-type and Omicron BA.1 vaccines. A total of eleven T-cell epitopes of wild-type and Omicron BA.1 spike were identified in BALB/c mice, and nine were identified in C57BL/6 mice, only two of which were CD4+ T-cell epitopes and most of which were CD8+ T-cell epitopes. The A67V and Del 69-70 mutations in Omicron BA.1 spike abolished one epitope in wild-type spike, and the T478K, E484A, Q493R, G496S and H655Y mutations resulted in three new epitopes in Omicron BA.1 spike, while the Y505H mutation did not affect the epitope. These data describe the difference of T-cell epitopes in SARS-CoV-2 wild-type and Omicron BA.1 spike in H-2b and H-2d mice, providing a better understanding of the effects of Omicron BA.1 spike mutations on cellular immunity. Full article
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12 pages, 6796 KiB  
Communication
SARS-CoV-2 Is More Efficient than HCoV-NL63 in Infecting a Small Subpopulation of ACE2+ Human Respiratory Epithelial Cells
by Gino Castillo, Rahul K. Nelli, Kruttika S. Phadke, Marlene Bravo-Parra, Juan Carlos Mora-Díaz, Bryan H. Bellaire and Luis G. Giménez-Lirola
Viruses 2023, 15(3), 736; https://doi.org/10.3390/v15030736 - 13 Mar 2023
Viewed by 1846
Abstract
Human coronavirus (HCoV)-NL63 is an important contributor to upper and lower respiratory tract infections, mainly in children, while severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can cause lower respiratory tract infections, and more severe, respiratory and systemic disease, [...] Read more.
Human coronavirus (HCoV)-NL63 is an important contributor to upper and lower respiratory tract infections, mainly in children, while severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can cause lower respiratory tract infections, and more severe, respiratory and systemic disease, which leads to fatal consequences in many cases. Using microscopy, immunohistochemistry (IHC), virus-binding assay, reverse transcriptase qPCR (RT-qPCR) assay, and flow cytometry, we compared the characteristics of the susceptibility, replication dynamics, and morphogenesis of HCoV-NL63 and SARS-CoV-2 in monolayer cultures of primary human respiratory epithelial cells (HRECs). Less than 10% HRECs expressed ACE2, and SARS-CoV-2 seemed much more efficient than HCoV-NL63 at infecting the very small proportion of HRECs expressing the ACE2 receptors. Furthermore, SARS-CoV-2 replicated more efficiently than HCoV-NL63 in HREC, which correlates with the cumulative evidence of the differences in their transmissibility. Full article
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10 pages, 2358 KiB  
Communication
Use of a Preclinical Natural Transmission Model to Study Antiviral Effects of a Carbohydrate-Binding Module Therapy against SARS-CoV-2 in Hamsters
by Daniel Knott, Rachel Fell, Jane A. Potter, Samantha Yuille, Franscisco J. Salguero, Victoria A. Graham, Roger Hewson, David Howat and Stuart D. Dowall
Viruses 2023, 15(3), 725; https://doi.org/10.3390/v15030725 - 11 Mar 2023
Viewed by 1395
Abstract
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and its expansion to a worldwide pandemic resulted in efforts to assess and develop interventions to reduce the disease burden. Despite the introduction of vaccine programmes against SARS-CoV-2, global incidence levels in early 2022 [...] Read more.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and its expansion to a worldwide pandemic resulted in efforts to assess and develop interventions to reduce the disease burden. Despite the introduction of vaccine programmes against SARS-CoV-2, global incidence levels in early 2022 remained high, demonstrating a need for the development of physiologically relevant models, which are essential for the identification of alternative antiviral strategies. The hamster model of SARS-CoV-2 infection has been widely adopted due to similarities with humans in terms of host cell entry mechanism (via ACE2), and aspects of symptomology and virus shedding. We have previously described a natural transmission hamster model that better represents the natural course of infection. In the present study, we have conducted further testing of the model using the first-in-class antiviral Neumifil, which has previously shown promise against SARS-CoV-2 after a direct intranasal challenge. Neumifil is an intranasally delivered carbohydrate-binding module (CBM) which reduces the binding of viruses to their cellular receptor. By targeting the host cell, Neumifil has the potential to provide broad protection against multiple pathogens and variants. This study demonstrates that using a combination of a prophylactic and therapeutic delivery of Neumifil significantly reduces the severity of clinical signs in animals infected via a natural route of transmission and indicates a reduction of viral loads in the upper respiratory tract. Further refinements of the model are required in order to ensure the adequate transmission of the virus. However, our results provide additional data to the evidence base of Neumifil efficacy against respiratory virus infection and demonstrate that the transmission model is a potentially valuable tool for testing antiviral compounds against SARS-CoV-2. Full article
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19 pages, 1077 KiB  
Review
SARS-CoV-2 Spike-Mediated Entry and Its Regulation by Host Innate Immunity
by Shi Yu, Huina Hu, Qiangyun Ai, Rong Bai, Kaixiong Ma, Minmin Zhou and Shaobo Wang
Viruses 2023, 15(3), 639; https://doi.org/10.3390/v15030639 - 27 Feb 2023
Cited by 1 | Viewed by 2810
Abstract
The constantly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) fuel the worldwide coronavirus disease (COVID-19) pandemic. The spike protein is essential for the SARS-CoV-2 viral entry and thus has been extensively targeted by therapeutic antibodies. However, mutations along [...] Read more.
The constantly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) fuel the worldwide coronavirus disease (COVID-19) pandemic. The spike protein is essential for the SARS-CoV-2 viral entry and thus has been extensively targeted by therapeutic antibodies. However, mutations along the spike in SARS-CoV-2 VOC and Omicron subvariants have caused more rapid spread and strong antigenic drifts, rendering most of the current antibodies ineffective. Hence, understanding and targeting the molecular mechanism of spike activation is of great interest in curbing the spread and development of new therapeutic approaches. In this review, we summarize the conserved features of spike-mediated viral entry in various SARS-CoV-2 VOC and highlight the converging proteolytic processes involved in priming and activating the spike. We also summarize the roles of innate immune factors in preventing spike-driven membrane fusion and provide outlines for the identification of novel therapeutics against coronavirus infections. Full article
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23 pages, 5984 KiB  
Article
SKI-1/S1P Facilitates SARS-CoV-2 Spike Induced Cell-to-Cell Fusion via Activation of SREBP-2 and Metalloproteases, Whereas PCSK9 Enhances the Degradation of ACE2
by Rachid Essalmani, Ursula Andréo, Alexandra Evagelidis, Maïlys Le Dévéhat, Oscar Henrique Pereira Ramos, Carole Fruchart Gaillard, Delia Susan-Resiga, Éric A. Cohen and Nabil G. Seidah
Viruses 2023, 15(2), 360; https://doi.org/10.3390/v15020360 - 27 Jan 2023
Cited by 4 | Viewed by 2344
Abstract
Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for the infectivity of SARS-CoV-2, which requires cleavage of its spike protein (S) at two sites: S1/S2 and S2′. This [...] Read more.
Proprotein convertases activate various envelope glycoproteins and participate in cellular entry of many viruses. We recently showed that the convertase furin is critical for the infectivity of SARS-CoV-2, which requires cleavage of its spike protein (S) at two sites: S1/S2 and S2′. This study investigates the implication of the two cholesterol-regulating convertases SKI-1 and PCSK9 in SARS-CoV-2 entry. The assays used were cell-to-cell fusion in HeLa cells and pseudoparticle entry into Calu-3 cells. SKI-1 increased cell-to-cell fusion by enhancing the activation of SREBP-2, whereas PCSK9 reduced cell-to-cell fusion by promoting the cellular degradation of ACE2. SKI-1 activity led to enhanced S2′ formation, which was attributed to increased metalloprotease activity as a response to enhanced cholesterol levels via activated SREBP-2. However, high metalloprotease activity resulted in the shedding of S2′ into a new C-terminal fragment (S2″), leading to reduced cell-to-cell fusion. Indeed, S-mutants that increase S2″ formation abolished S2′ and cell-to-cell fusion, as well as pseudoparticle entry, indicating that the formation of S2″ prevents SARS-CoV-2 cell-to-cell fusion and entry. We next demonstrated that PCSK9 enhanced the cellular degradation of ACE2, thereby reducing cell-to-cell fusion. However, different from the LDLR, a canonical target of PCSK9, the C-terminal CHRD domain of PCSK9 is dispensable for the PCSK9-induced degradation of ACE2. Molecular modeling suggested the binding of ACE2 to the Pro/Catalytic domains of mature PCSK9. Thus, both cholesterol-regulating convertases SKI-1 and PCSK9 can modulate SARS-CoV-2 entry via two independent mechanisms. Full article
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19 pages, 4916 KiB  
Article
Coronaviruses Are Abundant and Genetically Diverse in West and Central African Bats, including Viruses Closely Related to Human Coronaviruses
by Dowbiss Meta Djomsi, Audrey Lacroix, Abdoul Karim Soumah, Eddy Kinganda Lusamaki, Asma Mesdour, Raisa Raulino, Amandine Esteban, Innocent Ndong Bass, Flaubert Auguste Mba Djonzo, Souana Goumou, Simon Pierre Ndimbo-Kimugu, Guy Lempu, Placide Mbala Kingebeni, Daniel Mukadi Bamuleka, Jacques Likofata, Jean-Jacques Muyembe Tamfum, Abdoulaye Toure, Eitel Mpoudi Ngole, Charles Kouanfack, Eric Delaporte, Alpha Kabinet Keita, Steve Ahuka-Mundeke, Ahidjo Ayouba and Martine Peetersadd Show full author list remove Hide full author list
Viruses 2023, 15(2), 337; https://doi.org/10.3390/v15020337 - 25 Jan 2023
Cited by 4 | Viewed by 2348
Abstract
Bats are at the origin of human coronaviruses, either directly or via an intermediate host. We tested swabs from 4597 bats (897 from the Democratic Republic of Congo (DRC), 2191 from Cameroon and 1509 from Guinea) with a broadly reactive PCR in the [...] Read more.
Bats are at the origin of human coronaviruses, either directly or via an intermediate host. We tested swabs from 4597 bats (897 from the Democratic Republic of Congo (DRC), 2191 from Cameroon and 1509 from Guinea) with a broadly reactive PCR in the RdRp region. Coronaviruses were detected in 903 (19.6%) bats and in all species, with more than 25 individuals tested. The highest prevalence was observed in Eidolon helvum (239/733; 39.9%) and Rhinolophus sp. (306/899; 34.1%), followed by Hipposideros sp. (61/291; 20.9%). Frugivorous bats were predominantly infected with beta coronaviruses from the Nobecovirus subgenus (93.8%), in which at least 6 species/genus-specific subclades were observed. In contrast, insectivorous bats were infected with beta-coronaviruses from different subgenera (Nobecovirus (8.5%), Hibecovirus (32.8%), Merbecovirus (0.5%) and Sarbecovirus (57.6%)) and with a high diversity of alpha-coronaviruses. Overall, our study shows a high prevalence and genetic diversity of coronaviruses in bats and illustrates that Rhinolophus bats in Africa are infected at high levels with the Sarbecovirus subgenus, to which SARS-CoV-2 belongs. It is important to characterize in more detail the different coronavirus lineages from bats for their potential to infect human cells, their evolution and to study frequency and modes of contact between humans and bats in Africa. Full article
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2022

Jump to: 2024, 2023, 2021, 2020

10 pages, 980 KiB  
Brief Report
Clinical Severity in Different Waves of SARS-CoV-2 Infection in Sicily: A Model of Smith’s “Law of Declining Virulence” from Real-World Data
by Emanuele Amodio, Dario Genovese, Alessandra Fallucca, Patrizia Ferro, Benedetta Sparacia, Luciano D’Azzo, Angelo Fertitta, Carmelo Massimo Maida and Francesco Vitale
Viruses 2023, 15(1), 125; https://doi.org/10.3390/v15010125 - 31 Dec 2022
Cited by 6 | Viewed by 1946
Abstract
Background: The COVID-19 epidemic had a rapid spread worldwide with a continuous and fast mutation of the virus, resulting in the emergence of several variants of concern (VOC). The aim of this study was to evaluate the severity of each VOC among SARS-CoV-2 [...] Read more.
Background: The COVID-19 epidemic had a rapid spread worldwide with a continuous and fast mutation of the virus, resulting in the emergence of several variants of concern (VOC). The aim of this study was to evaluate the severity of each VOC among SARS-CoV-2 infected subjects by investigating deaths, ICU admissions, intubations, and severe critical symptoms. Methods: An ecological observational study was performed to evaluate mortality rates and clinical characteristics of 321,490 unvaccinated Sicilian SARS-CoV-2 cases observed from 2 March 2020 to 27 March 2022. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by multivariate logistic regression analysis evaluating factors determining a clinical worsening. Results: Delta (adj-OR 3.00, 95% Cls 2.70–3.33) and wild-type (adj-OR 2.41, 95% Cls 2.2–2.62) variants had a higher risk than the Omicron strain for developing critical COVID-19 necessitating intubation and eventually undergoing death. Moreover, males appeared to be significantly more susceptible to developing the worst clinical outcome considered, as did older subjects. Conclusions: The present study provides evidence of factors implicated in the worsening of SARS-CoV-2-infection-related clinical outcomes. The study highlighted the different roles of VOC, in particular Delta and wild-type, and being male and elderly in the development of a worse clinical outcome. Full article
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6 pages, 683 KiB  
Communication
Pharmacokinetic and Pharmacodynamic Effects of Polyclonal Antibodies against SARS-CoV2 in Mice
by Aruni Jha, Melanie Doyle-Eisele, David Revelli, Trevor Carnelley, Douglas Barker and Shantha Kodihalli
Viruses 2023, 15(1), 123; https://doi.org/10.3390/v15010123 - 30 Dec 2022
Cited by 2 | Viewed by 1717
Abstract
Despite ongoing vaccination efforts to prevent SARS-CoV-2 infections, treatment tools are still necessary to address the ongoing COVID-19 pandemic. We report here that COVID-HIGIV, a human immunoglobulin product for treatment of COVID-19, provided a significant survival benefit in SARS-CoV-2 infected transgenic mice compared [...] Read more.
Despite ongoing vaccination efforts to prevent SARS-CoV-2 infections, treatment tools are still necessary to address the ongoing COVID-19 pandemic. We report here that COVID-HIGIV, a human immunoglobulin product for treatment of COVID-19, provided a significant survival benefit in SARS-CoV-2 infected transgenic mice compared to controls. COVID-HIGIV also has similar pharmacokinetic profiles in healthy and SARS-CoV-2 infected mice over time after intravenous administration, with identical or comparable Tmax, Cmax, AUC0–∞ and Cl. AUC0–last increased and mean residence time, T1/2, and Vd reduced in infected animals compared to healthy animals. These data suggest that COVID-HIGIV may be an effective treatment for SARS-CoV-2 infection when given early after exposure. Full article
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15 pages, 2614 KiB  
Article
Epidemiology of Non-SARS-CoV2 Human Coronaviruses (HCoVs) in People Presenting with Influenza-like Illness (ILI) or Severe Acute Respiratory Infections (SARI) in Senegal from 2012 to 2020
by Modeste Name Faye, Mamadou Aliou Barry, Mamadou Malado Jallow, Serigne Fallou Wade, Marie Pedapa Mendy, Sara Sy, Amary Fall, Davy Evrard Kiori, Ndiende Koba Ndiaye, Deborah Goudiaby, Arfang Diamanka, Mbayame Ndiaye Niang and Ndongo Dia
Viruses 2023, 15(1), 20; https://doi.org/10.3390/v15010020 - 21 Dec 2022
Cited by 3 | Viewed by 1908
Abstract
In addition to emerging coronaviruses (SARS-CoV, MERS, SARS-CoV-2), there are seasonal human coronaviruses (HCoVs): HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1. With a wide distribution around the world, HCoVs are usually associated with mild respiratory disease. In the elderly, young children and immunocompromised patients, more [...] Read more.
In addition to emerging coronaviruses (SARS-CoV, MERS, SARS-CoV-2), there are seasonal human coronaviruses (HCoVs): HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1. With a wide distribution around the world, HCoVs are usually associated with mild respiratory disease. In the elderly, young children and immunocompromised patients, more severe or even fatal respiratory infections may be observed. In Africa, data on seasonal HCoV are scarce. This retrospective study investigated the epidemiology and genetic diversity of seasonal HCoVs during nine consecutive years of influenza-like illness surveillance in Senegal. Nasopharyngeal swabs were collected from ILI outpatients or from SARI hospitalized patients. HCoVs were diagnosed by qRT-PCR and the positive samples were selected for molecular characterization. Among 9337 samples tested for HCoV, 406 (4.3%) were positive: 235 (57.9%) OC43, 102 (25.1%) NL63, 58 (14.3%) 229E and 17 (4.2%) HKU1. The four types circulated during the study period and a peak was noted between November and January. Children under five were the most affected. Co-infections were observed between HCoV types (1.2%) or with other viruses (76.1%). Genetically, HCoVs types showed diversity. The results highlighted that the impact of HCoVs must be taken into account in public health; monitoring them is therefore particularly necessary both in the most sensitive populations and in animals. Full article
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8 pages, 1331 KiB  
Communication
Evaluation of Rapid Lateral-Flow Tests Directed against the SARS-CoV-2 Nucleoprotein Using Viral Suspensions Belonging to Different Lineages of SARS-CoV-2
by Sylvie Pillet, Julien Courtieux, Sylvie Gonzalo, Issam Bechri, Thomas Bourlet, Martine Valette, Antonin Bal and Bruno Pozzetto
Viruses 2022, 14(12), 2628; https://doi.org/10.3390/v14122628 - 25 Nov 2022
Cited by 1 | Viewed by 1164
Abstract
Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study [...] Read more.
Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study was to evaluate the ability of four rapid lateral-flow tests (RLFT) that were commercially available on the French market in 2022 to recognize various strains of SARS-CoV-2. Series of five-fold dilutions of seven viral suspensions belonging to different lineages of SARS-CoV-2 (19A, 20A, Alpha, Beta, Gamma, Delta and Omicron) were used to evaluate the analytical sensitivity of four commercially available RLFTs (manufacturers: Abbott, AAZ, Becton-Dickinson and Biospeedia). Cell culture and quantitative RT-PCR were used as references. Excellent correlations were observed for each lineage strain between the viral titer obtained via cell culture and the number of RNA copies measured by quantitative RT-PCR. Although the four tests were able to recognize all the tested variants, significant differences in terms of sensitivity were observed between the four RLFTs. Despite the limitation represented by the small number of devices and clinical isolates that were tested, this study contributed by rapidly comparing the sensitivity of SARS-CoV-2 RLFTs in the Omicron era. Full article
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12 pages, 2404 KiB  
Article
Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells
by Leo Yi Yang Lee, Randy Suryadinata, Conor McCafferty, Vera Ignjatovic, Damian F. J. Purcell, Phil Robinson, Craig J. Morton, Michael W. Parker, Gary P. Anderson, Paul Monagle, Kanta Subbarao and Jessica A. Neil
Viruses 2022, 14(12), 2620; https://doi.org/10.3390/v14122620 - 24 Nov 2022
Cited by 4 | Viewed by 2862
Abstract
SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for [...] Read more.
SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies. Full article
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13 pages, 2871 KiB  
Article
Prevalence of Human Coronaviruses in Children and Phylogenetic Analysis of HCoV-OC43 during 2016–2022 in Riyadh, Saudi Arabia
by Khalid A. Alamri, Mohamed A. Farrag, Ibrahim M. Aziz, Gani Asa Dudin, Arif Ahmed Mohammed and Fahad N. Almajhdi
Viruses 2022, 14(12), 2592; https://doi.org/10.3390/v14122592 - 22 Nov 2022
Cited by 2 | Viewed by 1813
Abstract
With the emergence of SARS-CoV-2, routine surveillance combined with sequence and phylogenetic analysis of coronaviruses is urgently required. In the current study, the four common human coronaviruses (HCoVs), OC43, NL63, HKU1, and 229E, were screened in 361 clinical samples collected from hospitalized children [...] Read more.
With the emergence of SARS-CoV-2, routine surveillance combined with sequence and phylogenetic analysis of coronaviruses is urgently required. In the current study, the four common human coronaviruses (HCoVs), OC43, NL63, HKU1, and 229E, were screened in 361 clinical samples collected from hospitalized children with respiratory symptoms during four winter seasons. RT-PCR-based detection and typing revealed different prevalence rates of HCoVs across the four seasons. Interestingly, none of the four HCoVs were detected in the samples (n = 100) collected during the winter season of the COVID-19 pandemic. HCoV-OC43 (4.15%) was the most frequently detected, followed by 229E (1.1%). Partial sequences of S and N genes of OC43 from the winter seasons of 2015/2016 and 2021/2022 were used for sequence and phylogenetic analysis. Multiple sequence alignment of the two Saudi OC43s strains with international strains revealed the presence of sequence deletions and several mutations, of which some changed their corresponding amino acids. Glycosylation profiles revealed a number of O-and N-glycosylation sites in both genes. Based on phylogenetic analysis, four genotypes were observed with Riyadh strains grouped into the genotype C. Further long-term surveillance with a large number of clinical samples and sequences is necessary to resolve the circulation patterns and evolutionary kinetics of OC43 in Saudi Arabia. Full article
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14 pages, 4105 KiB  
Article
New Insights into Avian Infectious Bronchitis Virus in Colombia from Whole-Genome Analysis
by Gloria Ramirez-Nieto, Daiana Mir, Diego Almansa-Villa, Geovanna Cordoba-Argotti, Magda Beltran-Leon, Nelida Rodriguez-Osorio, Jone Garai, Jovanny Zabaleta and Arlen P. Gomez
Viruses 2022, 14(11), 2562; https://doi.org/10.3390/v14112562 - 19 Nov 2022
Cited by 4 | Viewed by 2008
Abstract
Infectious Bronchitis (IB) is a respiratory disease caused by a highly variable Gammacoronavirus, which generates a negative impact on poultry health worldwide. GI-11 and GI-16 lineages have been identified in South America based on Infectious Bronchitis virus (IBV) partial S1 sequences. However, [...] Read more.
Infectious Bronchitis (IB) is a respiratory disease caused by a highly variable Gammacoronavirus, which generates a negative impact on poultry health worldwide. GI-11 and GI-16 lineages have been identified in South America based on Infectious Bronchitis virus (IBV) partial S1 sequences. However, full genome sequence information is limited. In this study we report, for the first time, the whole-genome sequence of IBV from Colombia. Seven IBV isolates obtained during 2012 and 2013 from farms with respiratory disease compatible with IB were selected and the complete genome sequence was obtained by NGS. According to S1 sequence phylogenetic analysis, six isolates belong to lineage GI-1 and one to lineage GVI-1. When whole genome was analyzed, five isolates were related to the vaccine strain Ma5 2016 and two showed mosaic genomes. Results from complete S1 sequence analysis provides further support for the hypothesis that GVI-1, considered a geographically confined lineage in Asia, could have originated in Colombia. Complete genome information reported in this research allow a deeper understanding of the phylogenetic evolution of variants and the recombination events between strains that are circulating worldwide, contributing to the knowledge of coronavirus in Latin America and the world. Full article
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14 pages, 784 KiB  
Review
Host Protective Immunity against Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) and the COVID-19 Vaccine-Induced Immunity against SARS-CoV-2 and Its Variants
by Rashed Noor
Viruses 2022, 14(11), 2541; https://doi.org/10.3390/v14112541 - 17 Nov 2022
Cited by 6 | Viewed by 2379
Abstract
The world is now apparently at the last/recovery stage of the COVID-19 pandemic, starting from 29 December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the progression of time, several mutations have taken place in the original SARS-CoV-2 Wuhan [...] Read more.
The world is now apparently at the last/recovery stage of the COVID-19 pandemic, starting from 29 December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the progression of time, several mutations have taken place in the original SARS-CoV-2 Wuhan strain, which have generated variants of concern (VOC). Therefore, combatting COVID-19 has required the development of COVID-19 vaccines using several platforms. The immunity induced by those vaccines is vital to study in order to assure total protection against SARS-CoV-2 and its emerging variants. Indeed, understanding and identifying COVID-19 protection mechanisms or the host immune responses are of significance in terms of designing both new and repurposed drugs as well as the development of novel vaccines with few to no side effects. Detecting the immune mechanisms for host protection against SARS-CoV-2 and its variants is crucial for the development of novel COVID-19 vaccines as well as to monitor the effectiveness of the currently used vaccines worldwide. Immune memory in terms of the production of neutralizing antibodies (NAbs) during reinfection is also very crucial to formulate the vaccine administration schedule/vaccine doses. The response of antigen-specific antibodies and NAbs as well as T cell responses, along with the protective cytokine production and the innate immunity generated upon COVID-19 vaccination, are discussed in the current review in comparison to the features of naturally induced protective immunity. Full article
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7 pages, 882 KiB  
Communication
An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant
by Haoran Zhang, Bing Hu, Panjing Lv, Yahui Liu, Meng Guo, Zhi Wu, Kangping Zhou, Minglu Dai, Xiao Yu, Zhang Liu, Bo Yu, Liqiong Xu, Min Guo, Kun Cai and Yan Li
Viruses 2022, 14(11), 2387; https://doi.org/10.3390/v14112387 - 28 Oct 2022
Cited by 2 | Viewed by 2024
Abstract
The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as [...] Read more.
The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as an ACE2 mimetic and a protein antagonist against SARS-CoV-2, which proved potent neutralization bioactivity on the Reference, Alpha, Beta, Delta, and Omicron strains of SARS-CoV-2. Since BA.5 is expected to rely on the interaction of the Spike complex with human ACE2 for cell entry, we reasonably assumed the lasting efficacy of the ACE2-mimicking Kansetin for neutralizing the new SARS-CoV-2 variant. The investigation was accordingly performed on in vitro Kansetin-Spike binding affinity by SPR and cell infection inhibition ability with pseudovirus and live virus assays. As a result, Kansetin showed dissociation constant KD and half inhibition concentration IC50 at the nanomolar to picomolar level, featuring a competent inhibition effect against the BA.5 sublineage. Conclusively, Kansetin is expected to be a promising therapeutic option against BA.5 and future SARS-CoV-2 sublineages. Full article
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13 pages, 1104 KiB  
Article
Association of the Transmembrane Serine Protease-2 (TMPRSS2) Polymorphisms with COVID-19
by Rosalinda Posadas-Sánchez, José Manuel Fragoso, Fausto Sánchez-Muñoz, Gustavo Rojas-Velasco, Julian Ramírez-Bello, Alberto López-Reyes, Laura E. Martínez-Gómez, Carlos Sierra-Fernández, Tatiana Rodríguez-Reyna, Nora Elemi Regino-Zamarripa, Gustavo Ramírez-Martínez, Joaquín Zuñiga-Ramos and Gilberto Vargas-Alarcón
Viruses 2022, 14(9), 1976; https://doi.org/10.3390/v14091976 - 7 Sep 2022
Cited by 10 | Viewed by 2530
Abstract
SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 [...] Read more.
SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 individuals negative for the SARS-CoV-2 infection confirmed by RT-PCR test and without antibodies anti-SARS-CoV-2. Four TMPRSS2 polymorphisms (rs12329760, rs2298659, rs456298, and rs462574) were determined using the 5′exonuclease TaqMan assays. Under different inheritance models, the rs2298659 (pcodominant2 = 0.018, precessive = 0.006, padditive = 0.019), rs456298 (pcodominant1 = 0.014, pcodominant2 = 0.004; pdominant = 0.009, precessive = 0.004, padditive = 0.0009), and rs462574 (pcodominant1 = 0.017, pcodominant2 = 0.004, pdominant = 0.041, precessive = 0.002, padditive = 0.003) polymorphisms were associated with high risk of developing COVID-19. Two risks (ATGC and GAAC) and two protectives (GAGC and GAGT) haplotypes were detected. High levels of lactic acid dehydrogenase (LDH) were observed in patients with the rs462574AA and rs456298TT genotypes (p = 0.005 and p = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574AA genotype (p = 0.028). Our data suggest that the rs2298659, rs456298, and rs462574 polymorphisms independently and as haplotypes are associated with the risk of COVID-19. The rs456298 and rs462574 genotypes are related to high levels of LDH and heart rate. Full article
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13 pages, 2863 KiB  
Article
Comparison of Physical and Biochemical Characterizations of SARS-CoV-2 Inactivated by Different Treatments
by Shouzhi Yu, Yangyang Wei, Hongyang Liang, Wenheng Ji, Zhen Chang, Siman Xie, Yichuan Wang, Wanli Li, Yingwei Liu, Hao Wu, Jie Li, Hui Wang and Xiaoming Yang
Viruses 2022, 14(9), 1938; https://doi.org/10.3390/v14091938 - 31 Aug 2022
Cited by 7 | Viewed by 2191 | Correction
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused huge social and economic distress. Given its rapid spread and the lack of specific treatment options, SARS-CoV-2 needs to be inactivated according to strict biosafety measures during laboratory diagnostics and vaccine development. The inactivation [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused huge social and economic distress. Given its rapid spread and the lack of specific treatment options, SARS-CoV-2 needs to be inactivated according to strict biosafety measures during laboratory diagnostics and vaccine development. The inactivation method for SARS-CoV-2 affects research related to the natural virus and its immune activity as an antigen in vaccines. In this study, we used size exclusion chromatography, western blotting, ELISA, an electron microscope, dynamic light scattering, circular dichroism, and surface plasmon resonance to evaluate the effects of four different chemical inactivation methods on the physical and biochemical characterization of SARS-CoV-2. Formaldehyde and β-propiolactone (BPL) treatment can completely inactivate the virus and have no significant effects on the morphology of the virus. None of the four tested inactivation methods affected the secondary structure of the virus, including the α-helix, antiparallel β-sheet, parallel β-sheet, β-turn, and random coil. However, formaldehyde and long-term BPL treatment (48 h) resulted in decreased viral S protein content and increased viral particle aggregation, respectively. The BPL treatment for 24 h can completely inactivate SARS-CoV-2 with the maximum retention of the morphology, physical properties, and the biochemical properties of the potential antigens of the virus. In summary, we have established a characterization system for the comprehensive evaluation of virus inactivation technology, which has important guiding significance for the development of vaccines against SARS-CoV-2 variants and research on natural SARS-CoV-2. Full article
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7 pages, 511 KiB  
Article
Regional Association between Mean Air Temperature and Case Numbers of Multiple SARS-CoV-2 Lineages throughout the Pandemic
by Camilla Mattiuzzi, Brandon M. Henry and Giuseppe Lippi
Viruses 2022, 14(9), 1913; https://doi.org/10.3390/v14091913 - 30 Aug 2022
Cited by 10 | Viewed by 1547
Abstract
The association between mean air temperature and new SARS-CoV-2 case numbers throughout the ongoing coronavirus disease 2019 (COVID-19) pandemic was investigated to identify whether diverse SARS-CoV-2 lineages may exhibit diverse environmental behaviors. The number of new COVID-19 daily cases in the province of [...] Read more.
The association between mean air temperature and new SARS-CoV-2 case numbers throughout the ongoing coronavirus disease 2019 (COVID-19) pandemic was investigated to identify whether diverse SARS-CoV-2 lineages may exhibit diverse environmental behaviors. The number of new COVID-19 daily cases in the province of Verona was obtained from the Veneto Regional Healthcare Service, whilst the mean daily air temperature during the same period was retrieved from the Regional Agency for Ambient Prevention and Protection of Veneto. A significant inverse correlation was found between new COVID-19 daily cases and mean air temperature in Verona up to Omicron BA.1/BA.2 predominance (correlation coefficients between −0.79 and −0.41). The correlation then became positive when the Omicron BA.4/BA.5 lineages were prevalent (r = 0.32). When the median value (and interquartile range; IQR) of new COVID-19 daily cases recorded during the warmer period of the year in Verona (June–July) was compared across the three years of the pandemic, a gradual increase could be seen over time, from 1 (IQR, 0–2) in 2020, to 22 (IQR, 11–113) in 2021, up to 890 (IQR, 343–1345) in 2022. These results suggest that measures for preventing SARS-CoV-2 infection should not be completely abandoned during the warmer periods of the year. Full article
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14 pages, 1756 KiB  
Article
SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition
by Melanie R. Walker, Daria Podlekareva, Stine Johnsen, Bonna Leerhøy, Cyrielle Fougeroux, Max Søgaard, Ali Salanti, Sisse Bolm Ditlev and Lea Barfod
Viruses 2022, 14(9), 1861; https://doi.org/10.3390/v14091861 - 24 Aug 2022
Cited by 3 | Viewed by 2116
Abstract
The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and [...] Read more.
The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern (VoCs), is needed. In this study, samples collected in Denmark early in the pandemic from paucisymptomatic subjects (n = 165) and symptomatic subjects (n = 57) infected with SARS-CoV-2 were used to assess IgG binding and inhibition in the form of angiotensin-converting enzyme 2 receptor (ACE2) competition against the wild-type and four SARS-CoV-2 VoCs (Alpha, Beta, Gamma, and Omicron). Antibodies induced early in the pandemic via natural infection were cross-reactive and inhibited ACE2 binding of the VoC, with reduced inhibition observed for the Omicron variant. When examined longitudinally, sustained cross-reactive inhibitory responses were found to exist in naturally infected paucisymptomatic subjects. After vaccination, receptor binding domain (RBD)-specific IgG binding increased by at least 3.5-fold and inhibition of ACE2 increased by at least 2-fold. When vaccination regimens were compared (two doses of Pfizer-BioNTech BNT162b2 (n = 50), or one dose of Oxford-AstraZeneca ChAdOx1 nCoV-19 followed by Pfizer-BioNTech BNT162b2 (ChAd/BNT) (n = 15)), higher levels of IgG binding and inhibition were associated with mix and match (ChAd/BNT) prime-boosting and time since vaccination. These results are particularly relevant for countries where vaccination levels are low. Full article
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11 pages, 2509 KiB  
Article
Development of a Genetically Engineered Bivalent Vaccine against Porcine Epidemic Diarrhea Virus and Porcine Rotavirus
by Wan Li, Mingkai Lei, Zhuofei Li, Huimin Li, Zheng Liu, Qigai He and Rui Luo
Viruses 2022, 14(8), 1746; https://doi.org/10.3390/v14081746 - 9 Aug 2022
Cited by 6 | Viewed by 3127
Abstract
Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute diarrhea, vomiting, dehydration, and a high mortality rate in neonatal piglets. In recent years, PEDV has been associated with co-infections with other swine enteric viruses, including porcine rotavirus (PoRV), resulting in [...] Read more.
Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute diarrhea, vomiting, dehydration, and a high mortality rate in neonatal piglets. In recent years, PEDV has been associated with co-infections with other swine enteric viruses, including porcine rotavirus (PoRV), resulting in increased mortality among newborn piglets. In this paper, we developed a bivalent vaccine against PEDV and PoRV by constructing a recombinant PEDV encoding PoRV VP7 (rPEDV-PoRV-VP7). The recombinant virus was constructed by replacing the entire open reading frame 3 (ORF3) in the genome of an attenuated PEDV strain YN150 with the PoRV VP7 gene using reverse genetic systems. Similar plaque morphology and replication kinetics were observed in Vero cells with the recombinant PEDV compared to the wild-type PEDV. It is noteworthy that the VP7 protein could be expressed stably in rPEDV-PoRV-VP7-infected cells. To evaluate the immunogenicity and safety of rPEDV-PoRV-VP7, 10-day-old piglets were vaccinated with the recombinant virus. After inoculation, no piglet displayed clinical symptoms such as vomiting, diarrhea, or anorexia. The PoRV VP7- and PEDV spike-specific IgG in serum and IgA in saliva were detected in piglets after rPEDV-PoRV-VP7 vaccination. Moreover, both PoRV and PEDV neutralizing antibodies were produced simultaneously in the inoculated piglets. Collectively, we engineered a recombinant PEDV expressing PoRV VP7 that could be used as an effective bivalent vaccine against PEDV and PoRV. Full article
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10 pages, 1980 KiB  
Communication
Distinct Antibody Responses to Endemic Coronaviruses Pre- and Post-SARS-CoV-2 Infection in Kenyan Infants and Mothers
by Caitlin I. Stoddard, Kevin Sung, Ednah Ojee, Judith Adhiambo, Emily R. Begnel, Jennifer Slyker, Soren Gantt, Frederick A. Matsen IV, John Kinuthia, Dalton Wamalwa, Julie Overbaugh and Dara A. Lehman
Viruses 2022, 14(7), 1517; https://doi.org/10.3390/v14071517 - 12 Jul 2022
Cited by 7 | Viewed by 1847
Abstract
Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, which is the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and [...] Read more.
Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, which is the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers; however, we observed a very modest association between pre-existing HCoV-229E antibody levels and a lack of SARS-CoV-2 seroconversion in the infants. After seroconversion to SARS-CoV-2, antibody binding titers to the endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not the endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in the mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in the infants, suggesting the increase seen in the mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both the mothers and infants, both of whom were unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we found evidence of increased eHCoV antibody levels following SARS-CoV-2 seroconversion in the mothers but not the infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants. Full article
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14 pages, 2942 KiB  
Article
Human ACE2 Polymorphisms from Different Human Populations Modulate SARS-CoV-2 Infection
by Pan Hu, Vanessa L. Bauer, Sara L. Sawyer and Felipe Diaz-Griffero
Viruses 2022, 14(7), 1451; https://doi.org/10.3390/v14071451 - 30 Jun 2022
Cited by 3 | Viewed by 2337
Abstract
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 6 million deaths worldwide. The high variability in COVID-19 symptoms remains one of the most interesting mysteries of the pandemic. Genetic and environmental factors are likely to [...] Read more.
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 6 million deaths worldwide. The high variability in COVID-19 symptoms remains one of the most interesting mysteries of the pandemic. Genetic and environmental factors are likely to be key determinants of COVID-19 symptomatology. Here, we explored ACE2 as a genetic determinant for SARS-CoV-2 infection and COVID-19 symptomatology. Each human genome encodes two alleles of ACE2, which encodes the cell entry receptor for SARS-CoV-2. Here, we determined whether naturally occurring human ACE2 (hACE2) polymorphisms in the human population affect SARS-CoV-2 infection and the severity of COVID-19 symptoms. ACE2 variants S19P, I21V, E23K, K26R, K31R, N33I, H34R, E35K, and T92I showed increased virus infection compared to wild-type ACE2; thus, these variants could increase the risk for COVID-19. In contrast, variants D38V, Y83H, I468V, and N638S showed reduced infection, indicating a potential protective effect. hACE2 variants K26R and T92I increased infection by three-fold without changing the levels of ACE2 on the surface of the cells, suggesting that these variants may increase the risk of severe COVID-19. On the contrary, hACE2 variants D38V and Y83H decreased SARS-CoV-2 infection by four- and ten-fold, respectively, without changing surface expression, suggesting that these variants may protect against severe COVID-19. Remarkably, all protective hACE2 Polymorphisms were found almost exclusively in Asian populations, which may provide a partial explanation for the low COVID-19 mortality rates in Asian countries. Thus, hACE2 polymorphisms may modulate susceptibility to SARS-CoV-2 in the host and partially account for the differences in severity of COVID-19 among different ethnic groups. Full article
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18 pages, 757 KiB  
Article
Weekly Nowcasting of New COVID-19 Cases Using Past Viral Load Measurements
by Athar Khalil, Khalil Al Handawi, Zeina Mohsen, Afif Abdel Nour, Rita Feghali, Ibrahim Chamseddine and Michael Kokkolaras
Viruses 2022, 14(7), 1414; https://doi.org/10.3390/v14071414 - 28 Jun 2022
Cited by 3 | Viewed by 1949
Abstract
The rapid spread of the coronavirus disease COVID-19 has imposed clinical and financial burdens on hospitals and governments attempting to provide patients with medical care and implement disease-controlling policies. The transmissibility of the disease was shown to be correlated with the patient’s viral [...] Read more.
The rapid spread of the coronavirus disease COVID-19 has imposed clinical and financial burdens on hospitals and governments attempting to provide patients with medical care and implement disease-controlling policies. The transmissibility of the disease was shown to be correlated with the patient’s viral load, which can be measured during testing using the cycle threshold (Ct). Previous models have utilized Ct to forecast the trajectory of the spread, which can provide valuable information to better allocate resources and change policies. However, these models combined other variables specific to medical institutions or came in the form of compartmental models that rely on epidemiological assumptions, all of which could impose prediction uncertainties. In this study, we overcome these limitations using data-driven modeling that utilizes Ct and previous number of cases, two institution-independent variables. We collected three groups of patients (n = 6296, n = 3228, and n = 12,096) from different time periods to train, validate, and independently validate the models. We used three machine learning algorithms and three deep learning algorithms that can model the temporal dynamic behavior of the number of cases. The endpoint was 7-week forward number of cases, and the prediction was evaluated using mean square error (MSE). The sequence-to-sequence model showed the best prediction during validation (MSE = 0.025), while polynomial regression (OLS) and support vector machine regression (SVR) had better performance during independent validation (MSE = 0.1596, and MSE = 0.16754, respectively), which exhibited better generalizability of the latter. The OLS and SVR models were used on a dataset from an external institution and showed promise in predicting COVID-19 incidences across institutions. These models may support clinical and logistic decision-making after prospective validation. Full article
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18 pages, 3684 KiB  
Article
Characterization of the Cross-Species Transmission Potential for Porcine Deltacoronaviruses Expressing Sparrow Coronavirus Spike Protein in Commercial Poultry
by Moyasar A. Alhamo, Patricia A. Boley, Mingde Liu, Xiaoyu Niu, Kush Kumar Yadav, Carolyn Lee, Linda J. Saif, Qiuhong Wang and Scott P. Kenney
Viruses 2022, 14(6), 1225; https://doi.org/10.3390/v14061225 - 5 Jun 2022
Cited by 4 | Viewed by 2694
Abstract
Avian species often serve as transmission vectors and sources of recombination for viral infections due to their ability to travel vast distances and their gregarious behaviors. Recently a novel deltacoronavirus (DCoV) was identified in sparrows. Sparrow deltacoronavirus (SpDCoV), coupled with close contact between [...] Read more.
Avian species often serve as transmission vectors and sources of recombination for viral infections due to their ability to travel vast distances and their gregarious behaviors. Recently a novel deltacoronavirus (DCoV) was identified in sparrows. Sparrow deltacoronavirus (SpDCoV), coupled with close contact between sparrows and swine carrying porcine deltacoronavirus (PDCoV) may facilitate recombination of DCoVs resulting in novel CoV variants. We hypothesized that the spike (S) protein or receptor-binding domain (RBD) from sparrow coronaviruses (SpCoVs) may enhance infection in poultry. We used recombinant chimeric viruses, which express S protein or the RBD of SpCoV (icPDCoV-SHKU17, and icPDCoV-RBDISU) on the genomic backbone of an infectious clone of PDCoV (icPDCoV). Chimeric viruses were utilized to infect chicken derived DF-1 cells, turkey poults, and embryonated chicken eggs (ECEs) to examine permissiveness, viral replication kinetics, pathogenesis and pathology. We demonstrated that DF-1 cells in addition to the positive control LLC-PK1 cells are susceptible to SpCoV spike- and RBD- recombinant chimeric virus infections. However, the replication of chimeric viruses in DF-1 cells, but not LLC-PK1 cells, was inefficient. Inoculated 8-day-old turkey poults appeared resistant to icPDCoV-, icPDCoV-SHKU17- and icPDCoV-RBDISU virus infections. In 5-day-old ECEs, significant mortality was observed in PDCoV inoculated eggs with less in the spike chimeras, while in 11-day-old ECEs there was no evidence of viral replication, suggesting that PDCoV is better adapted to cross species infection and differentiated ECE cells are not susceptible to PDCoV infection. Collectively, we demonstrate that the SpCoV chimeric viruses are not more infectious in turkeys, nor ECEs than wild type PDCoV. Therefore, understanding the cell and host factors that contribute to resistance to PDCoV and avian-swine chimeric virus infections may aid in the design of novel antiviral therapies against DCoVs. Full article
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16 pages, 6108 KiB  
Article
Non-Productive Infection of Glial Cells with SARS-CoV-2 in Hamster Organotypic Cerebellar Slice Cultures
by Lise Lamoureux, Babu Sajesh, Jessy A. Slota, Sarah J. Medina, Matthew Mayor, Kathy L. Frost, Bryce Warner, Kathy Manguiat, Heidi Wood, Darwyn Kobasa and Stephanie A. Booth
Viruses 2022, 14(6), 1218; https://doi.org/10.3390/v14061218 - 3 Jun 2022
Viewed by 2476
Abstract
The numerous neurological syndromes associated with COVID-19 implicate an effect of viral pathogenesis on neuronal function, yet reports of direct SARS-CoV-2 infection in the brain are conflicting. We used a well-established organotypic brain slice culture to determine the permissivity of hamster brain tissues [...] Read more.
The numerous neurological syndromes associated with COVID-19 implicate an effect of viral pathogenesis on neuronal function, yet reports of direct SARS-CoV-2 infection in the brain are conflicting. We used a well-established organotypic brain slice culture to determine the permissivity of hamster brain tissues to SARS-CoV-2 infection. We found levels of live virus waned after inoculation and observed no evidence of cell-to-cell spread, indicating that SARS-CoV-2 infection was non-productive. Nonetheless, we identified a small number of infected cells with glial phenotypes; however, no evidence of viral infection or replication was observed in neurons. Our data corroborate several clinical studies that have assessed patients with COVID-19 and their association with neurological involvement. Full article
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10 pages, 1222 KiB  
Article
Longitudinal Analysis of Coronavirus-Neutralizing Activity in COVID-19 Patients
by Florian D. Hastert, Lisa Henss, Christine von Rhein, Julia Gerbeth, Imke Wieters, Frauke Borgans, Yascha Khodamoradi, Kai Zacharowski, Gernot Rohde, Maria J.G.T. Vehreschild and Barbara S. Schnierle
Viruses 2022, 14(5), 882; https://doi.org/10.3390/v14050882 - 23 Apr 2022
Cited by 2 | Viewed by 3383
Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has now been continuing for more than two years. The infection causes COVID-19, a disease of the respiratory and cardiovascular system of variable severity. Here, the humoral immune response of 80 COVID-19 patients from the [...] Read more.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has now been continuing for more than two years. The infection causes COVID-19, a disease of the respiratory and cardiovascular system of variable severity. Here, the humoral immune response of 80 COVID-19 patients from the University Hospital Frankfurt/Main, Germany, was characterized longitudinally. The SARS-CoV-2 neutralization activity of serum waned over time. The neutralizing potential of serum directed towards the human alpha-coronavirus NL-63 (NL63) also waned, indicating that no cross-priming against alpha-coronaviruses occurred. A subset of the recovered patients (n = 13) was additionally vaccinated with the mRNA vaccine Comirnaty. Vaccination increased neutralization activity against SARS-CoV-2 wild-type (WT), Delta, and Omicron, although Omicron-specific neutralization was not detectable prior to vaccination. In addition, the vaccination induced neutralizing antibodies against the more distantly related SARS-CoV-1 but not against NL63. The results indicate that although SARS-CoV-2 humoral immune responses induced by infection wane, vaccination induces a broad neutralizing activity against multiple SARS-CoVs, but not to the common cold alpha-coronavirus NL63. Full article
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18 pages, 1333 KiB  
Article
Longitudinal Survey of Coronavirus Circulation and Diversity in Insectivorous Bat Colonies in Zimbabwe
by Vimbiso Chidoti, Hélène De Nys, Valérie Pinarello, Getrude Mashura, Dorothée Missé, Laure Guerrini, Davies Pfukenyi, Julien Cappelle, Ngoni Chiweshe, Ahidjo Ayouba, Gift Matope, Martine Peeters, Elizabeth Gori, Mathieu Bourgarel and Florian Liégeois
Viruses 2022, 14(4), 781; https://doi.org/10.3390/v14040781 - 9 Apr 2022
Cited by 8 | Viewed by 3250
Abstract
Background: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. Methods: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat–human [...] Read more.
Background: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. Methods: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat–human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems. Results: Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively. Conclusions: The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe. Full article
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14 pages, 1570 KiB  
Perspective
TP53 Gene Therapy as a Potential Treatment for Patients with COVID-19
by Joe B. Harford, Sang Soo Kim, Kathleen F. Pirollo and Esther H. Chang
Viruses 2022, 14(4), 739; https://doi.org/10.3390/v14040739 - 31 Mar 2022
Cited by 19 | Viewed by 3368
Abstract
SGT-53 is a novel investigational agent that comprises an immunoliposome carrying a plasmid vector driving expression of the human TP53 gene that encodes wild-type human p53. SGT-53 is currently in phase II human trials for advanced pancreatic cancer. Although p53 is best known [...] Read more.
SGT-53 is a novel investigational agent that comprises an immunoliposome carrying a plasmid vector driving expression of the human TP53 gene that encodes wild-type human p53. SGT-53 is currently in phase II human trials for advanced pancreatic cancer. Although p53 is best known as a tumor suppressor, its participation in both innate and adaptive immune responses is well documented. It is now clear that p53 is an important component of the host response to various viral infections. To facilitate their viral life cycles, viruses have developed a diverse repertoire of strategies for counteracting the antiviral activities of host immune system by manipulating p53-dependent pathways in host cells. Coronaviruses reduce endogenous p53 levels in the cells they infect by enhancing the degradation of p53 in proteasomes. Thus, interference with p53 function is an important component in viral pathogenesis. Transfection of cells by SGT-53 has been shown to transiently produce exogenous p53 that is active as a pleiotropic transcription factor. We herein summarize the rationale for repurposing SGT-53 as a therapy for infection by SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Because p53 regulation was found to play a crucial role in different infection stages of a wide variety of viruses, it is rational to believe that restoring p53 function based on SGT-53 treatment may lead to beneficial therapeutic outcomes for infectious disease at large including heretofore unknown viral pathogens that may emerge in the future. Full article
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16 pages, 2856 KiB  
Article
Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection
by Ailyn C. Ramón, George V. Pérez, Evelin Caballero, Mauro Rosales, Daylén Aguilar, Dania Vázquez-Blomquist, Yassel Ramos, Arielis Rodríguez-Ulloa, Viviana Falcón, María Pilar Rodríguez-Moltó, Ke Yang, Yasser Perera and Silvio E. Perea
Viruses 2022, 14(3), 552; https://doi.org/10.3390/v14030552 - 7 Mar 2022
Cited by 3 | Viewed by 2306
Abstract
Coronaviruses constitute a global threat to the human population; therefore, effective pan-coronavirus antiviral drugs are required to tackle future re-emerging virus outbreaks. Protein kinase CK2 has been suggested as a promising therapeutic target in COVID-19 owing to the in vitro antiviral activity observed [...] Read more.
Coronaviruses constitute a global threat to the human population; therefore, effective pan-coronavirus antiviral drugs are required to tackle future re-emerging virus outbreaks. Protein kinase CK2 has been suggested as a promising therapeutic target in COVID-19 owing to the in vitro antiviral activity observed after both pharmacologic and genetic inhibition of the enzyme. Here, we explored the putative antiviral effect of the anti-CK2 peptide CIGB-325 on bovine coronavirus (BCoV) infection using different in vitro viral infected cell-based assays. The impact of the peptide on viral mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. Finally, pull-down experiments followed by Western blot and/or mass spectrometry analysis were performed to identify CIGB-325-interacting proteins. We found that CIGB-325 inhibited both the cytopathic effect and the number of plaque-forming units. Accordingly, intracellular viral protein levels were clearly reduced after treatment of BCoV-infected cells, with CIGB-325 determined by immunocytochemistry. Pull-down assay data revealed the physical interaction of CIGB-325 with viral nucleocapsid (N) protein and a group of bona fide CK2 cellular substrates. Our findings evidence in vitro antiviral activity of CIGB-325 against bovine coronavirus as well as some molecular clues that might support such effect. Altogether, data provided here strengthen the rationale of inhibiting CK2 to treat betacoronavirus infections. Full article
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13 pages, 1338 KiB  
Article
Antibody Evaluation and Mutations of Antigenic Epitopes in the Spike Protein of the Porcine Epidemic Diarrhea Virus from Pig Farms with Repeated Intentional Exposure (Feedback)
by Thu Hien Nguyen Thi, Chi-Chih Chen, Wen-Bin Chung, Hso-Chi Chaung, Yen-Li Huang, Li-Ting Cheng and Guan-Ming Ke
Viruses 2022, 14(3), 551; https://doi.org/10.3390/v14030551 - 7 Mar 2022
Cited by 2 | Viewed by 2283
Abstract
The feedback strategy, or controlled exposure of pig herd to the porcine epidemic diarrhea virus (PEDV), significantly decreased losses during a severe outbreak in late 2013 in Taiwan. However, some pig farms still suffered from recurrent outbreaks. To evaluate the association between antibody [...] Read more.
The feedback strategy, or controlled exposure of pig herd to the porcine epidemic diarrhea virus (PEDV), significantly decreased losses during a severe outbreak in late 2013 in Taiwan. However, some pig farms still suffered from recurrent outbreaks. To evaluate the association between antibody titers and clinical manifestations, sera and colostra were analyzed from one pig farm that employed the feedback strategy. Furthermore, spike (S) gene full sequences from six positive samples of two farms with and without using feedback were compared to investigate the evolution of PEDV variants circulating in pig herds. The results in this study showed that high PEDV antibody titers do not correlate with the high rate of protection from PEDV infection. In addition, repeated feedback generated the emergence of PEDV variants with unique substitutions of N537S and Y561H in the COE domain and S769F in the SS6 epitopes. These mutations indicated the pathogenetic evolution of PEDV strains existing in the cycle of the feedback method. A very strict biosecurity practice to block the routes of pathogen transfer should be followed to achieve successful control of PEDV infections in pig herds. Full article
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17 pages, 2882 KiB  
Article
Direct Lysis RT-qPCR of SARS-CoV-2 in Cell Culture Supernatant Allows for Fast and Accurate Quantification
by Nicky Craig, Sarah L. Fletcher, Alison Daniels, Caitlin Newman, Marie O’Shea, Wenfang Spring Tan, Amanda Warr and Christine Tait-Burkard
Viruses 2022, 14(3), 508; https://doi.org/10.3390/v14030508 - 28 Feb 2022
Cited by 7 | Viewed by 4460
Abstract
Studying the entire virus replication cycle of SARS-CoV-2 is essential to identify the host factors involved and treatments to combat infection. Quantification of released virions often requires lengthy procedures, whereas quantification of viral RNA in supernatant is faster and applicable to clinical isolates. [...] Read more.
Studying the entire virus replication cycle of SARS-CoV-2 is essential to identify the host factors involved and treatments to combat infection. Quantification of released virions often requires lengthy procedures, whereas quantification of viral RNA in supernatant is faster and applicable to clinical isolates. Viral RNA purification is expensive in terms of time and resources, and is often unsuitable for high-throughput screening. Direct lysis protocols were explored for patient swab samples, but the lack of virus inactivation, cost, sensitivity, and accuracy is hampering their application and usefulness for in vitro studies. Here, we show a highly sensitive, accurate, fast, and cheap direct lysis RT-qPCR method for quantification of SARS-CoV-2 in culture supernatant. This method inactivates the virus and permits detection limits of 0.043 TCID50 virus and <1.89 copy RNA template per reaction. Comparing direct lysis with RNA extraction, a mean difference of +0.69 ± 0.56 cycles was observed. Application of the method to established qPCR methods for RSV (-ve RNA), IAV (segmented -ve RNA), and BHV (dsDNA) showed wider applicability to other enveloped viruses, whereby IAV showed poorer sensitivity. This shows that accurate quantification of SARS-CoV-2 and other enveloped viruses can be achieved using direct lysis protocols, facilitating a wide range of high- and low-throughput applications. Full article
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7 pages, 2263 KiB  
Brief Report
Isolation and Genomic Characterization of SARS-CoV-2 Omicron Variant Obtained from Human Clinical Specimens
by Pragya D. Yadav, Nivedita Gupta, Varsha Potdar, Sreelekshmy Mohandas, Rima R. Sahay, Prasad Sarkale, Anita M. Shete, Alpana Razdan, Deepak Y. Patil, Dimpal A. Nyayanit, Yash Joshi, Savita Patil, Triparna Majumdar, Hitesh Dighe, Bharti Malhotra, Jayanthi Shastri and Priya Abraham
Viruses 2022, 14(3), 461; https://doi.org/10.3390/v14030461 - 24 Feb 2022
Cited by 9 | Viewed by 2651
Abstract
Due to the failure of virus isolation of the Omicron variant in Vero CCL-81 from the clinical specimens of COVID-19 cases, an initial in vivo and subsequent in vitro approach was utilized for the isolation of the virus. A total of 74 oropharyngeal/nasopharyngeal [...] Read more.
Due to the failure of virus isolation of the Omicron variant in Vero CCL-81 from the clinical specimens of COVID-19 cases, an initial in vivo and subsequent in vitro approach was utilized for the isolation of the virus. A total of 74 oropharyngeal/nasopharyngeal specimens were collected from SARS-CoV-2 positive international travellers and a contact case at Delhi and Mumbai, India. All the specimens were sequenced using next-generation sequencing and simultaneously inoculated onto Vero CCL-81 cells for virus isolation. Subsequently, two omicron positive specimens were inoculated into Syrian hamsters for two passages. The initial passage of the positive hamster specimens was inoculated onto Vero CCL-81 cells. The clinical specimens, hamster specimens, and Vero CCL-81 passages were sequenced to assess the mutational changes in different host species. The replication of the Omicron variant in hamsters was confirmed with the presence of a high viral load in nasal turbinate and lung specimens of both passages. The successful isolation of the virus from hamster specimens with Vero CCL-81 was observed with cytopathic effect in infected cells and high viral load in the cell suspension. The genome analysis revealed the presence of L212C mutation, Tyrosine 69 deletion, and C25000T nucleotide change in spike gene of hamster passage sequences and an absence of V17I mutation in E gene in hamster passage sequences, unlike human clinical specimen and Vero CCL-81 passages. No change was observed in the furin cleavage site in any of the specimen sequences, suggesting intact pathogenicity of the virus isolate. Our data demonstrated successful isolation of the Omicron variant with the in vivo method first followed by in vitro method. The virus isolate could be used in the future to explore different aspects of the Omicron variant. Full article
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37 pages, 50150 KiB  
Review
Known Cellular and Receptor Interactions of Animal and Human Coronaviruses: A Review
by Holly Everest, Phoebe Stevenson-Leggett, Dalan Bailey, Erica Bickerton and Sarah Keep
Viruses 2022, 14(2), 351; https://doi.org/10.3390/v14020351 - 8 Feb 2022
Cited by 11 | Viewed by 4799
Abstract
This article aims to review all currently known interactions between animal and human coronaviruses and their cellular receptors. Over the past 20 years, three novel coronaviruses have emerged that have caused severe disease in humans, including SARS-CoV-2 (severe acute respiratory syndrome virus 2); [...] Read more.
This article aims to review all currently known interactions between animal and human coronaviruses and their cellular receptors. Over the past 20 years, three novel coronaviruses have emerged that have caused severe disease in humans, including SARS-CoV-2 (severe acute respiratory syndrome virus 2); therefore, a deeper understanding of coronavirus host–cell interactions is essential. Receptor-binding is the first stage in coronavirus entry prior to replication and can be altered by minor changes within the spike protein—the coronavirus surface glycoprotein responsible for the recognition of cell-surface receptors. The recognition of receptors by coronaviruses is also a major determinant in infection, tropism, and pathogenesis and acts as a key target for host-immune surveillance and other potential intervention strategies. We aim to highlight the need for a continued in-depth understanding of this subject area following on from the SARS-CoV-2 pandemic, with the possibility for more zoonotic transmission events. We also acknowledge the need for more targeted research towards glycan–coronavirus interactions as zoonotic spillover events from animals to humans, following an alteration in glycan-binding capability, have been well-documented for other viruses such as Influenza A. Full article
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12 pages, 2151 KiB  
Article
Alphacoronaviruses Are Common in Bats in the Upper Midwestern United States
by Reagan Schaeffer, Gun Temeeyasen and Ben M. Hause
Viruses 2022, 14(2), 184; https://doi.org/10.3390/v14020184 - 19 Jan 2022
Cited by 2 | Viewed by 2684
Abstract
Bats are a reservoir for coronaviruses (CoVs) that periodically spill over to humans, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. A collection of 174 bat samples originating from South Dakota, Minnesota, Iowa, and Nebraska submitted for rabies virus testing [...] Read more.
Bats are a reservoir for coronaviruses (CoVs) that periodically spill over to humans, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. A collection of 174 bat samples originating from South Dakota, Minnesota, Iowa, and Nebraska submitted for rabies virus testing due to human exposure were analyzed using a pan-coronavirus PCR. A previously partially characterized CoV, Eptesicus bat CoV, was identified in 12 (6.9%) samples by nested RT-PCR. Six near-complete genomes were determined. Genetic analysis found a high similarity between all CoV-positive samples, Rocky Mountain bat CoV 65 and alphacoronavirus HCQD-2020 recently identified in South Korea. Phylogenetic analysis of genome sequences showed EbCoV is closely related to bat CoV HKU2 and swine acute diarrhea syndrome CoV; however, topological incongruences were noted for the spike gene that was more closely related to porcine epidemic diarrhea virus. Similar to some alphaCoVs, a novel gene, ORF7, was discovered downstream of the nucleocapsid, whose protein lacked similarity to known proteins. The widespread circulation of EbCoV with similarities to bat viruses that have spilled over to swine warrants further surveillance. Full article
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14 pages, 2058 KiB  
Article
GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition
by Eloïne Bestion, Keivan Zandi, Sandrine Belouzard, Julien Andreani, Hubert Lepidi, Marie Novello, Clara Rouquairol, Jean-Pierre Baudoin, Madani Rachid, Bernard La Scola, Jean-Louis Mege, Jean Dubuisson, Raymond F. Schinazi, Soraya Mezouar and Philippe Halfon
Viruses 2022, 14(1), 132; https://doi.org/10.3390/v14010132 - 12 Jan 2022
Cited by 12 | Viewed by 2844
Abstract
Since December 2019, SARS-CoV-2 has spread quickly worldwide, leading to more than 280 million confirmed cases, including over 5,000,000 deaths. Interestingly, coronaviruses were found to subvert and hijack autophagic process to allow their viral replication. Autophagy-modulating compounds thus rapidly emerged as an attractive [...] Read more.
Since December 2019, SARS-CoV-2 has spread quickly worldwide, leading to more than 280 million confirmed cases, including over 5,000,000 deaths. Interestingly, coronaviruses were found to subvert and hijack autophagic process to allow their viral replication. Autophagy-modulating compounds thus rapidly emerged as an attractive strategy to fight SARS-CoV-2 infection, including the well-known chloroquine (CQ). Here, we investigated the antiviral activity and associated mechanism of GNS561/Ezurpimtrostat, a small lysosomotropic molecule inhibitor of late-stage autophagy. Interestingly, GNS561 exhibited antiviral activity of 6–40 nM depending on the viral strain considered, currently positioning it as the most powerful molecule investigated in SARS-CoV-2 infection. We then showed that GNS561 was located in lysosome-associated-membrane-protein-2-positive (LAMP2-positive) lysosomes, together with SARS-CoV-2. Moreover, GNS561 increased LC3-II spot size and caused the accumulation of autophagic vacuoles and the presence of multilamellar bodies, suggesting that GNS561 disrupted the autophagy mechanism. To confirm our findings, we used the K18-hACE2 mouse model and highlighted that GNS561 treatment led to a decline in SARS-CoV-2 virions in the lungs associated with a disruption of the autophagy pathway. Overall, our study highlights GNS561 as a powerful drug in the treatment of SARS-CoV-2 infection and supports the hypothesis that autophagy blockers could be an alternative strategy for COVID-19. Full article
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2021

Jump to: 2024, 2023, 2022, 2020

12 pages, 2277 KiB  
Article
SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response
by Wen-qing Su, Xue-jie Yu and Chuan-min Zhou
Viruses 2021, 13(12), 2467; https://doi.org/10.3390/v13122467 - 9 Dec 2021
Cited by 24 | Viewed by 4316
Abstract
In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for [...] Read more.
In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral life cycle, the underlying autophagy-inducing mechanisms remain largely unexplored. Using several autophagy-deficient cell lines and autophagy inhibitors, we demonstrated that SARS-CoV-2 ORF3a was able to induce incomplete autophagy in a FIP200/Beclin-1-dependent manner. Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19. Full article
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17 pages, 2978 KiB  
Article
Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection
by Huawei Xia, Zeming Zhang and Fuping You
Viruses 2021, 13(12), 2383; https://doi.org/10.3390/v13122383 - 28 Nov 2021
Cited by 17 | Viewed by 4873
Abstract
Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We [...] Read more.
Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection. Full article
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15 pages, 1490 KiB  
Article
Apoptosis Enhances the Replication of Human Coronavirus OC43
by Sony Maharjan, Mijeong Kang, Jinsoo Kim, Dongbum Kim, Sangkyu Park, Minyoung Kim, Kyeongbin Baek, Younghee Lee and Hyung-Joo Kwon
Viruses 2021, 13(11), 2199; https://doi.org/10.3390/v13112199 - 1 Nov 2021
Cited by 8 | Viewed by 3081
Abstract
Human coronavirus OC43 (HCoV-OC43) is one of the coronaviruses causing a mild common cold, but few studies have been made on this strain. Here, we identified the molecular mechanisms involved in HCoV-OC43-induced apoptosis and its implications for viral reproduction in Vero cells and [...] Read more.
Human coronavirus OC43 (HCoV-OC43) is one of the coronaviruses causing a mild common cold, but few studies have been made on this strain. Here, we identified the molecular mechanisms involved in HCoV-OC43-induced apoptosis and its implications for viral reproduction in Vero cells and MRC-5 cells. HCoV-OC43 infection induced apoptosis that was accompanied by cleavage of caspase-3 and PARP, degradation of cyclin D1, and cell cycle arrest at S and G2M phases. Dephosphorylation of STAT1 and STAT3, induced by HCoV-OC43 infection, was also associated with HCoV-OC43-mediated apoptosis. The pan-caspase inhibitor effectively prevented HCoV-OC43-induced apoptosis and reduced viral replication, suggesting that apoptosis contributes to viral replication. Collectively our results indicate that HCoV-OC43 induces caspase-dependent apoptosis to promote viral replication in Vero cells and MRC-5 cells. Full article
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11 pages, 16352 KiB  
Brief Report
Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
by Yuyong Zhou, Karen A. Gammeltoft, Andrea Galli, Anna Offersgaard, Ulrik Fahnøe, Santseharay Ramirez, Jens Bukh and Judith M. Gottwein
Viruses 2021, 13(10), 2082; https://doi.org/10.3390/v13102082 - 15 Oct 2021
Cited by 20 | Viewed by 3567
Abstract
We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, rimantadine was most potent followed by memantine and amantadine (50% effective concentrations: 36, 80 and 116 µM, respectively). Rimantadine [...] Read more.
We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, rimantadine was most potent followed by memantine and amantadine (50% effective concentrations: 36, 80 and 116 µM, respectively). Rimantadine also showed the highest selectivity index, followed by amantadine and memantine (17.3, 12.2 and 7.6, respectively). Similar results were observed in human hepatoma Huh7.5 and lung carcinoma A549-hACE2 cells. Inhibitors interacted in a similar antagonistic manner with remdesivir and had a similar barrier to viral escape. Rimantadine acted mainly at the viral post-entry level and partially at the viral entry level. Based on these results, rimantadine showed the most promise for treatment of SARS-CoV-2. Full article
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10 pages, 1228 KiB  
Article
Development of a Recombinant RBD Subunit Vaccine for SARS-CoV-2
by Yi-Sheng Sun, Jing-Jing Zhou, Han-Ping Zhu, Fang Xu, Wen-Bin Zhao, Hang-Jing Lu, Zhen Wang, Shu-Qing Chen, Ping-Ping Yao, Jian-Min Jiang and Zhan Zhou
Viruses 2021, 13(10), 1936; https://doi.org/10.3390/v13101936 - 26 Sep 2021
Cited by 10 | Viewed by 3798
Abstract
The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 [...] Read more.
The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19. Full article
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12 pages, 2086 KiB  
Article
Multiple Occurrences of a 168-Nucleotide Deletion in SARS-CoV-2 ORF8, Unnoticed by Standard Amplicon Sequencing and Variant Calling Pipelines
by David Brandt, Marina Simunovic, Tobias Busche, Markus Haak, Peter Belmann, Sebastian Jünemann, Tizian Schulz, Levin Joe Klages, Svenja Vinke, Michael Beckstette, Ehmke Pohl, Christiane Scherer, Alexander Sczyrba and Jörn Kalinowski
Viruses 2021, 13(9), 1870; https://doi.org/10.3390/v13091870 - 18 Sep 2021
Cited by 6 | Viewed by 5437
Abstract
Genomic surveillance of the SARS-CoV-2 pandemic is crucial and mainly achieved by amplicon sequencing protocols. Overlapping tiled-amplicons are generated to establish contiguous SARS-CoV-2 genome sequences, which enable the precise resolution of infection chains and outbreaks. We investigated a SARS-CoV-2 outbreak in a local [...] Read more.
Genomic surveillance of the SARS-CoV-2 pandemic is crucial and mainly achieved by amplicon sequencing protocols. Overlapping tiled-amplicons are generated to establish contiguous SARS-CoV-2 genome sequences, which enable the precise resolution of infection chains and outbreaks. We investigated a SARS-CoV-2 outbreak in a local hospital and used nanopore sequencing with a modified ARTIC protocol employing 1200 bp long amplicons. We detected a long deletion of 168 nucleotides in the ORF8 gene in 76 samples from the hospital outbreak. This deletion is difficult to identify with the classical amplicon sequencing procedures since it removes two amplicon primer-binding sites. We analyzed public SARS-CoV-2 sequences and sequencing read data from ENA and identified the same deletion in over 100 genomes belonging to different lineages of SARS-CoV-2, pointing to a mutation hotspot or to positive selection. In almost all cases, the deletion was not represented in the virus genome sequence after consensus building. Additionally, further database searches point to other deletions in the ORF8 coding region that have never been reported by the standard data analysis pipelines. These findings and the fact that ORF8 is especially prone to deletions, make a clear case for the urgent necessity of public availability of the raw data for this and other large deletions that might change the physiology of the virus towards endemism. Full article
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17 pages, 40146 KiB  
Article
Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease
by Yue Zhang, Huijie Chen, Mengmeng Zou, Rick Oerlemans, Changhao Shao, Yudong Ren, Ruili Zhang, Xiaodan Huang, Guangxing Li and Yingying Cong
Viruses 2021, 13(9), 1825; https://doi.org/10.3390/v13091825 - 14 Sep 2021
Cited by 18 | Viewed by 3408
Abstract
The porcine epidemic diarrhea virus (PEDV) is an Alphacoronavirus (α-CoV) that causes high mortality in infected piglets, resulting in serious economic losses in the farming industry. Hypericin is a dianthrone compound that has been shown as an antiviral activity on several viruses. Here, [...] Read more.
The porcine epidemic diarrhea virus (PEDV) is an Alphacoronavirus (α-CoV) that causes high mortality in infected piglets, resulting in serious economic losses in the farming industry. Hypericin is a dianthrone compound that has been shown as an antiviral activity on several viruses. Here, we first evaluated the antiviral effect of hypericin in PEDV and found the viral replication and egression were significantly reduced with hypericin post-treatment. As hypericin has been shown in SARS-CoV-2 that it is bound to viral 3CLpro, we thus established a molecular docking between hypericin and PEDV 3CLpro using different software and found hypericin bound to 3CLpro through two pockets. These binding pockets were further verified by another docking between hypericin and PEDV 3CLpro pocket mutants, and the fluorescence resonance energy transfer (FRET) assay confirmed that hypericin inhibits the PEDV 3CLpro activity. Moreover, the alignments of α-CoV 3CLpro sequences or crystal structure revealed that the pockets mediating hypericin and PEDV 3CLpro binding were highly conserved, especially in transmissible gastroenteritis virus (TGEV). We then validated the anti-TGEV effect of hypericin through viral replication and egression. Overall, our results push forward that hypericin was for the first time shown to have an inhibitory effect on PEDV and TGEV by targeting 3CLpro, and it deserves further attention as not only a pan-anti-α-CoV compound but potentially also as a compound of other coronaviral infections. Full article
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7 pages, 501 KiB  
Brief Report
Prevalence of Neutralising Antibodies to HCoV-NL63 in Healthy Adults in Australia
by Sean A. Lynch, Kanta Subbarao, Siddhartha Mahanty, Bridget E. Barber, Eileen V. Roulis, Lia van der Hoek, James S. McCarthy and Kirsten M. Spann
Viruses 2021, 13(8), 1618; https://doi.org/10.3390/v13081618 - 16 Aug 2021
Cited by 3 | Viewed by 3052
Abstract
The COVID-19 pandemic has highlighted the importance of understanding the immune response to seasonal human coronavirus (HCoV) infections such as HCoV-NL63, how existing neutralising antibodies to HCoV may modulate responses to SARS-CoV-2 infection, and the utility of seasonal HCoV as human challenge models. [...] Read more.
The COVID-19 pandemic has highlighted the importance of understanding the immune response to seasonal human coronavirus (HCoV) infections such as HCoV-NL63, how existing neutralising antibodies to HCoV may modulate responses to SARS-CoV-2 infection, and the utility of seasonal HCoV as human challenge models. Therefore, in this study we quantified HCoV-NL63 neutralising antibody titres in a healthy adult population using plasma from 100 blood donors in Australia. A microneutralisation assay was performed with plasma diluted from 1:10 to 1:160 and tested with the HCoV-NL63 Amsterdam-1 strain. Neutralising antibodies were detected in 71% of the plasma samples, with a median geometric mean titre of 14. This titre was similar to those reported in convalescent sera taken from individuals 3–7 months following asymptomatic SARS-CoV-2 infection, and 2–3 years post-infection from symptomatic SARS-CoV-1 patients. HCoV-NL63 neutralising antibody titres decreased with increasing age (R2 = 0.042, p = 0.038), but did not differ by sex. Overall, this study demonstrates that neutralising antibody to HCoV-NL63 is detectable in approximately 71% of the healthy adult population of Australia. Similar titres did not impede the use of another seasonal human coronavirus (HCoV-229E) in a human challenge model, thus, HCoV-NL63 may be useful as a human challenge model for more pathogenic coronaviruses. Full article
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13 pages, 1491 KiB  
Article
Epidemiology and Seasonality of Endemic Human Coronaviruses in South African and Zambian Children: A Case-Control Pneumonia Study
by Vicky L. Baillie, David P. Moore, Azwifarwi Mathunjwa, Daniel E. Park, Donald M. Thea, Geoffrey Kwenda, Lawrence Mwananyanda and Shabir A. Madhi
Viruses 2021, 13(8), 1513; https://doi.org/10.3390/v13081513 - 31 Jul 2021
Cited by 8 | Viewed by 2203
Abstract
Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high [...] Read more.
Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2–2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and –HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May–August). There was no association between HIV status and endemic HCoV detection. Full article
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7 pages, 644 KiB  
Communication
Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines
by Yong Yang, Jinkai Zang, Shiqi Xu, Xueyang Zhang, Sule Yuan, Haikun Wang, Dimitri Lavillette, Chao Zhang and Zhong Huang
Viruses 2021, 13(8), 1421; https://doi.org/10.3390/v13081421 - 22 Jul 2021
Cited by 6 | Viewed by 2855
Abstract
The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of [...] Read more.
The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate. Full article
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12 pages, 558 KiB  
Article
Human Coronaviruses Do Not Transfer Efficiently between Surfaces in the Absence of Organic Materials
by Matthew Dallner, Jennifer Harlow and Neda Nasheri
Viruses 2021, 13(7), 1352; https://doi.org/10.3390/v13071352 - 13 Jul 2021
Cited by 16 | Viewed by 4280
Abstract
Human coronaviruses, including SARS-CoV-2, are known to spread mainly via close contact and respiratory droplets. However, other potential means of transmission may be present. Fomite-mediated transmission occurs when viruses are deposited onto a surface and then transfer to a subsequent individual. Surfaces can [...] Read more.
Human coronaviruses, including SARS-CoV-2, are known to spread mainly via close contact and respiratory droplets. However, other potential means of transmission may be present. Fomite-mediated transmission occurs when viruses are deposited onto a surface and then transfer to a subsequent individual. Surfaces can become contaminated directly from respiratory droplets or from a contaminated hand. Due to mask mandates in many countries around the world, the former is less likely. Hands can become contaminated if respiratory droplets are deposited on them (i.e., coughing or sneezing) or through contact with fecal material where human coronaviruses (HCoVs) can be shed. The focus of this paper is on whether human coronaviruses can transfer efficiently from contaminated hands to food or food contact surfaces. The surfaces chosen were: stainless steel, plastic, cucumber and apple. Transfer was first tested with cellular maintenance media and three viruses: two human coronaviruses, 229E and OC43, and murine norovirus-1, as a surrogate for human norovirus. There was no transfer for either of the human coronaviruses to any of the surfaces. Murine norovirus-1 did transfer to stainless steel, cucumber and apple, with transfer efficiencies of 9.19%, 5.95% and 0.329%, respectively. Human coronavirus OC43 transfer was then tested in the presence of fecal material, and transfer was observed for stainless steel (0.52%), cucumber (19.82%) and apple (15.51%) but not plastic. This study indicates that human coronaviruses do not transfer effectively from contaminated hands to contact surfaces without the presence of fecal material. Full article
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21 pages, 2968 KiB  
Review
Anti-SARS-CoV-2 Vaccines and Monoclonal Antibodies Facing Viral Variants
by Ahlam Chaqroun, Cédric Hartard and Evelyne Schvoerer
Viruses 2021, 13(6), 1171; https://doi.org/10.3390/v13061171 - 18 Jun 2021
Cited by 24 | Viewed by 5147
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is genetically variable, allowing it to adapt to various hosts including humans. Indeed, SARS-CoV-2 has accumulated around two mutations per genome each month. The first relevant event in this context was the occurrence of the [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is genetically variable, allowing it to adapt to various hosts including humans. Indeed, SARS-CoV-2 has accumulated around two mutations per genome each month. The first relevant event in this context was the occurrence of the mutant D614G in the Spike gene. Moreover, several variants have emerged, including the well-characterized 20I/501Y.V1, 20H/501Y.V2, and 20J/501Y.V3 strains, in addition to those that have been detected within clusters, such as 19B/501Y or 20C/655Y in France. Mutants have also emerged in animals, including a variant transmitted to humans, namely, the Mink variant detected in Denmark. The emergence of these variants has affected the transmissibility of the virus (for example, 20I/501Y.V1, which was up to 82% more transmissible than other preexisting variants), its severity, and its ability to escape natural, adaptive, vaccine, and therapeutic immunity. In this respect, we review the literature on variants that have currently emerged, and their effect on vaccines and therapies, and, in particular, monoclonal antibodies (mAbs). The emergence of SARS-CoV-2 variants must be examined to allow effective preventive and curative control strategies to be developed. Full article
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7 pages, 2608 KiB  
Article
Evaluation of Production Lots of a Rapid Point-of-Care Lateral Flow Serological Test Intended for Identification of IgM and IgG against the N-Terminal Part of the Spike Protein (S1) of SARS-CoV-2
by Tove Hoffman, Linda Kolstad, Bengt Rönnberg and Åke Lundkvist
Viruses 2021, 13(6), 1043; https://doi.org/10.3390/v13061043 - 31 May 2021
Cited by 5 | Viewed by 3007