Highly Pathogenic Viruses: Challenges for Diagnostics Development and Drug Discovery

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (20 October 2023) | Viewed by 22153

Special Issue Editors

Department of Molecular Medicine, University of Padova, 35122 Padova, Italy
Interests: emerging zoonotic viruses; highly pathogenic viruses; virus/host interactions; antiviral discovery; molecular diagnostics and surveillance
Department of Molecular Medicine, University of Padova, 35122 Padova, Italy
Interests: viruses; antivirals; non canonical targets; pathogenic mechanism; secondary structures

Special Issue Information

Dear Colleague,

Emerging and re-emerging viral infections have increased in frequency over the last decade. Old and new pathogens, classified as biosafety level (BSL) 3 and 4 pathogenic viruses, have occurred causing outbreaks and pandemics, such as the Ebola virus in Africa and the severe acute respiratory syndrome coronavirus 2 worldwide. To date, no approved therapeutics are available to counter many of these pathogens; furthermore, the availability/accessibility of diagnostic tools is frequently limited. More efforts are needed to increase preparedness—based on surveillance and diagnostics—and to promote discovery and development of drugs to fight known and unknown emerging viruses.

This Special Issue aims to collect reviews and research articles focusing on:

(i) new diagnostics
(ii) well-established viral models and molecular tools for drug discovery
(iii) innovative technologies in drug discovery for highly pathogenic viruses
(iv) new strategies to overcome the limitations imposed by the manipulation of highly pathogenic viruses in BSL-3 and -4 facilities
(v) biosafety issues in diagnostics development and drug discovery

We look forward to your contributions.

Prof. Dr. Cristiano Salata
Dr. Ilaria Frasson
Guest Editors

Manuscript Submission Information

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Keywords

  • highly pathogenic viruses
  • diagnostics
  • drug discovery
  • prepardness
  • epidemiology
  • therapeutics
  • biosafety

Published Papers (7 papers)

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Research

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15 pages, 3495 KiB  
Article
Antiviral Activity of Oligonucleotides Targeting the SARS-CoV-2 Genomic RNA Stem-Loop Sequences within the 3′-End of the ORF1b
by Maria Alfreda Stincarelli, Arianna Rocca, Alberto Antonelli, Gian Maria Rossolini and Simone Giannecchini
Pathogens 2022, 11(11), 1286; https://doi.org/10.3390/pathogens11111286 - 01 Nov 2022
Cited by 2 | Viewed by 1286
Abstract
Increased evidence shows vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited no long-term efficacy and limited worldwide availability, while existing antivirals and treatment options have only limited efficacy. In this study, the main objective was the development of antiviral strategies using [...] Read more.
Increased evidence shows vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited no long-term efficacy and limited worldwide availability, while existing antivirals and treatment options have only limited efficacy. In this study, the main objective was the development of antiviral strategies using nucleic acid-based molecules. To this purpose, partially overlapped 6-19-mer phosphorothioate deoxyoligonucleotides (S-ONs) designed on the SARS-CoV-2 genomic RNA stem-loop packaging sequences within the 3′ end of the ORF1b were synthetized using the direct and complementary sequence. Among the S-ONs tested, several oligonucleotides exhibited a fifty percent inhibitory concentration antiviral activity ranging from 0.27 to 34 μM, in the absence of cytotoxicity. The S-ON with a scrambled sequence used in the same conditions was not active. Moreover, selected 10-mer S-ONs were tested using different infectious doses and against different SARS-CoV-2 variants, showing comparable antiviral activity that was abrogated when the central sequence was mutated. Experiments to evaluate the intracellular functional target localization of the S-ON inhibitory activity were also performed. Collectively the data indicate that the SARS-CoV-2 packaging region in the 3′ end of the ORF1b may be a promising target candidate for further investigation to develop innovative nucleic-acid-based antiviral therapy. Full article
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11 pages, 821 KiB  
Article
Diagnostic Laboratory Characteristics of COVID-19 Patients Infected by Fomites: COVID-19 Outbreak in a South Korean Public Administrative Facility
by Se-Min Hwang, Yoomi Jung and Haesook Seo
Pathogens 2022, 11(6), 700; https://doi.org/10.3390/pathogens11060700 - 17 Jun 2022
Cited by 1 | Viewed by 1496
Abstract
There is a paucity of data regarding the differentiating characteristics of patients who were infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by fomites around the world. We conducted an event-based outbreak investigation, involving 795 public officers and 277 assistant staff, in [...] Read more.
There is a paucity of data regarding the differentiating characteristics of patients who were infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by fomites around the world. We conducted an event-based outbreak investigation, involving 795 public officers and 277 assistant staff, in the Ministry of Oceans and Fisheries (MOF) or the same building from March 2 to March 18, 2020. The SARS-CoV-2 patients were found to have more frequently touched fomites and used public toilets than those who were tested negative for the virus (cOR, 24.38; 95% CI, 4.95–120.01). Symptoms such as coughing and loss of taste and smell were more frequently found in the office-cleaner group than in the public-officer group. The SARS-CoV-2 office-cleaner patients were more likely to have a high RdRp(Ct) value of PCR (median: 34.17 vs. 24.99; p = 0.035) and E(Ct) value of PCR (median: 32.30 vs. 24.74; p = 0.045). All office cleaner patients (100%) had a ground glass opacity in both lobes. Regarding segmental lung involvement of CT, two patients (100%) had a lesion in the right middle lobe, which invaded the whole lobe later. This implies that the fomite might be a selective risk factor of SARS-CoV-2 infection. Full article
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14 pages, 1149 KiB  
Article
Cranberry (Vaccinium macrocarpon) Extract Impairs Nairovirus Infection by Inhibiting the Attachment to Target Cells
by Mattia Mirandola, Maria Vittoria Salvati, Carola Rodigari, K. Sofia Appelberg, Ali Mirazimi, Massimo E. Maffei, Giorgio Gribaudo and Cristiano Salata
Pathogens 2021, 10(8), 1025; https://doi.org/10.3390/pathogens10081025 - 13 Aug 2021
Cited by 4 | Viewed by 2311
Abstract
Hazara virus (HAZV) belongs to the Nairoviridae family and is included in the same serogroup of the Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is the most widespread tick-borne arbovirus. It is responsible for a serious hemorrhagic disease, for which specific and effective treatment [...] Read more.
Hazara virus (HAZV) belongs to the Nairoviridae family and is included in the same serogroup of the Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is the most widespread tick-borne arbovirus. It is responsible for a serious hemorrhagic disease, for which specific and effective treatment and preventive systems are missing. Bioactive compounds derived from several natural products may provide a natural source of broad-spectrum antiviral agents, characterized by good tolerability and minimal side effects. Previous in vitro studies have shown that a cranberry (Vaccinium macrocarpon Ait.) extract containing a high content of A-type proanthocyanidins (PAC-A) inhibits the replication of herpes simplex and influenza viruses by hampering their attachment to target cells. Given the broad-spectrum antimicrobial activity of polyphenols and the urgency to develop therapies for the treatment of CCHF, we investigated the antiviral activity of cranberry extract against HAZV, a surrogate nairovirus model of CCHFV that can be handled in Level 2 Biosafety Laboratories (BSL-2). The results indicate that the cranberry extract exerts an antiviral activity against HAZV by targeting early stages of the viral replication cycle, including the initial adsorption to target cells. Although the details of the molecular mechanism of action remain to be clarified, the cranberry extract exerts a virucidal effect through a direct interaction with HAZV particles that leads to the subsequent impairment of virus attachment to cell-surface receptors. Finally, the antiviral activity of the cranberry extract was also confirmed for CCHFV. As a whole, the evidence obtained suggests that cranberry extract is a valuable candidate to be considered for the development of therapeutic strategies for CCHFV infections. Full article
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Review

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13 pages, 911 KiB  
Review
In Silico Evaluation of CRISPR-Based Assays for Effective Detection of SARS-CoV-2
by Pornchai Kaewsapsak, Naphat Chantaravisoot, Pattaraporn Nimsamer, Oraphan Mayuramart, Suwanan Mankhong and Sunchai Payungporn
Pathogens 2022, 11(9), 968; https://doi.org/10.3390/pathogens11090968 - 25 Aug 2022
Cited by 1 | Viewed by 1728
Abstract
Coronavirus disease (COVID-19) caused by the SARS-CoV-2 has been an outbreak since late 2019 up to now. This pandemic causes rapid development in molecular detection technologies to diagnose viral infection for epidemic prevention. In addition to antigen test kit (ATK) and polymerase chain [...] Read more.
Coronavirus disease (COVID-19) caused by the SARS-CoV-2 has been an outbreak since late 2019 up to now. This pandemic causes rapid development in molecular detection technologies to diagnose viral infection for epidemic prevention. In addition to antigen test kit (ATK) and polymerase chain reaction (PCR), CRISPR-based assays for detection of SARS-CoV-2 have gained attention because it has a simple setup but still maintain high specificity and sensitivity. However, the SARS-CoV-2 has been continuing mutating over the past few years. Thus, molecular tools that rely on matching at the nucleotide level need to be reevaluated to preserve their specificity and sensitivity. Here, we analyzed how mutations in different variants of concern (VOC), including Alpha, Beta, Gamma, Delta, and Omicron strains, could introduce mismatches to the previously reported primers and crRNAs used in the CRISPR-Cas system. Over 40% of the primer sets and 15% of the crRNAs contain mismatches. Hence, primers and crRNAs in nucleic acid-based assays must be chosen carefully to pair up with SARS-CoV-2 variants. In conclusion, the data obtained from this study could be useful in selecting the conserved primers and crRNAs for effective detections against the VOC of SARS-CoV-2. Full article
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7 pages, 478 KiB  
Review
Prevention and Control of COVID-19 after Resuming General Hospital Functions
by Jingwen Li, Hanshu Liu, Chao Duan, Lan Chen, Qing Zhang, Xi Fang, Lei Tan, Na Li, Xinyi Wang, Xing Zhang, Chunmei Li, Zhicheng Lin and Nian Xiong
Pathogens 2022, 11(4), 452; https://doi.org/10.3390/pathogens11040452 - 10 Apr 2022
Cited by 2 | Viewed by 1681
Abstract
During the COVID-19 pandemic, many general hospitals have been transformed into designated infectious disease care facilities, where a large number of patients with COVID-19 infections have been treated and discharged. With declines in the number of hospitalizations, a major question for our healthcare [...] Read more.
During the COVID-19 pandemic, many general hospitals have been transformed into designated infectious disease care facilities, where a large number of patients with COVID-19 infections have been treated and discharged. With declines in the number of hospitalizations, a major question for our healthcare systems, especially for these designated facilities, is how to safely resume hospital function after these patients have been discharged. Here, we take a designated COVID-19-care facility in Wuhan, China, as an example to share our experience in resuming hospital function while ensuring the safety of patients and medical workers. After more than 1200 patients with COVID-19 infections were discharged in late March, 2020, our hospital resumed function by setting up a three-level hospital infection management system with four grades of risk of exposure. Moreover, we also took measures to ensure the safety of medical personnel in different departments including clinics, wards, and operation rooms. After all patients with COVID-19 infections were discharged, during the five months of regular function from April to September in 2020, no positive cases have been found among more than 40,000 people in our hospital, including hospital staff and patients. Full article
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25 pages, 435 KiB  
Review
Methods of Inactivation of Highly Pathogenic Viruses for Molecular, Serology or Vaccine Development Purposes
by Simon Elveborg, Vanessa M. Monteil and Ali Mirazimi
Pathogens 2022, 11(2), 271; https://doi.org/10.3390/pathogens11020271 - 19 Feb 2022
Cited by 30 | Viewed by 8744
Abstract
The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic [...] Read more.
The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic viruses are represented by enveloped RNA viruses belonging to the Togaviridae, Flaviviridae, Filoviridae, Arenaviridae, Hantaviridae, Peribunyaviridae, Phenuiviridae, Nairoviridae and Orthomyxoviridae families. Here, we summarize inactivation methods for these virus families that allow for subsequent molecular and serological analysis or vaccine development. The techniques identified here include: treatment with guanidium-based chaotropic salts, heat inactivation, photoactive compounds such as psoralens or 1.5-iodonaphtyl azide, detergents, fixing with aldehydes, UV-radiation, gamma irradiation, aromatic disulfides, beta-propiolacton and hydrogen peroxide. The combination of simple techniques such as heat or UV-radiation and detergents such as Tween-20, Triton X-100 or Sodium dodecyl sulfate are often sufficient for virus inactivation, but the efficiency may be affected by influencing factors including quantity of infectious particles, matrix constitution, pH, salt- and protein content. Residual infectivity of the inactivated virus could have disastrous consequences for both laboratory/healthcare personnel and patients. Therefore, the development of inactivation protocols requires careful considerations which we review here. Full article
27 pages, 26742 KiB  
Review
Inhibition of Viral Membrane Fusion by Peptides and Approaches to Peptide Design
by Nejat Düzgüneş, Narcis Fernandez-Fuentes and Krystyna Konopka
Pathogens 2021, 10(12), 1599; https://doi.org/10.3390/pathogens10121599 - 09 Dec 2021
Cited by 14 | Viewed by 3719
Abstract
Fusion of lipid-enveloped viruses with the cellular plasma membrane or the endosome membrane is mediated by viral envelope proteins that undergo large conformational changes following binding to receptors. The HIV-1 fusion protein gp41 undergoes a transition into a “six-helix bundle” after binding of [...] Read more.
Fusion of lipid-enveloped viruses with the cellular plasma membrane or the endosome membrane is mediated by viral envelope proteins that undergo large conformational changes following binding to receptors. The HIV-1 fusion protein gp41 undergoes a transition into a “six-helix bundle” after binding of the surface protein gp120 to the CD4 receptor and a co-receptor. Synthetic peptides that mimic part of this structure interfere with the formation of the helix structure and inhibit membrane fusion. This approach also works with the S spike protein of SARS-CoV-2. Here we review the peptide inhibitors of membrane fusion involved in infection by influenza virus, HIV-1, MERS and SARS coronaviruses, hepatitis viruses, paramyxoviruses, flaviviruses, herpesviruses and filoviruses. We also describe recent computational methods used for the identification of peptide sequences that can interact strongly with protein interfaces, with special emphasis on SARS-CoV-2, using the PePI-Covid19 database. Full article
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