Viral Entry Inhibitors 2022

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 31732

Special Issue Editors

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
Interests: antiviral drugs; coronaviruses; influenza viruses; HIV; immunology
New York Blood Center, New York, NY, USA
Interests: antiviral drugs; HIV; coronaviruses; immunology; entry inhibitor
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Interests: structural biology; cryo-electron microscopy; antiviral drugs; entry inhibitor; coronaviruses

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our new Special Issue, “Viral Entry Inhibitor”. Virus entry into the host target cell is the earliest step in the replication cycle of both enveloped and non-enveloped viruses. A virus entry inhibitor is an antiviral agent that interferes with the binding between a viral surface protein and a receptor on the host cell or blocks fusion between viral and host cell membranes, and inhibits entry of the viral genetic materials into the host cell. Virus entry inhibitors take effect before viral genome release, making them good candidates for development as pre- and post-exposure prophylaxis, microbicides, and therapeutics.

This Special Issue aims to provides an advanced forum for antiviral studies, including (but not limited to) peptide-, small molecule-, protein-, and antibody-based entry inhibitors, especially broad-spectrum viral entry inhibitors. We hope that this Special Issue will provide more therapeutic options for emerging viruses in the future and insights to viral entry mechanisms.

In this Special Issue, original research articles, reviews, and commentaries related to our topics are welcome. Research areas may include (but are not limited to) the following: 1) identification of a novel viral entry inhibitor; 2) mechanism study on a viral entry inhibitor; 3) modification of a viral entry inhibitor; 4) clinical trial of a viral entry inhibitor; 5) future trend of antivirals.

We look forward to receiving your contributions.

Prof. Dr. Shuwen Liu
Dr. Shan Su
Dr. Yun Zhu
Guest Editors

Manuscript Submission Information

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Keywords

  • viral entry
  • entry inhibitor
  • viral surface protein
  • broad-spectrum inhibitor
  • protease inhibitor
  • endocytosis inhibitor
  • clinical trial
  • small molecule
  • peptide
  • antibody

Published Papers (13 papers)

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Research

Jump to: Review

21 pages, 3232 KiB  
Article
Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process
by Yingna Huang, Yinyan Li, Zhixuan Chen, Liurong Chen, Jinlong Liang, Chunyu Zhang, Zhengyin Zhang and Jie Yang
Viruses 2022, 14(12), 2738; https://doi.org/10.3390/v14122738 - 08 Dec 2022
Cited by 5 | Viewed by 1710
Abstract
Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. [...] Read more.
Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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11 pages, 2647 KiB  
Article
Screening and Identification of Lassa Virus Entry Inhibitors from a Fragment-Based Drug Discovery Library
by Yuxia Hou, Yang Liu, Xiaoying Jia, Minmin Zhou, Wenting Mao, Siqi Dong, Yueli Zhang, Gengfu Xiao and Wei Wang
Viruses 2022, 14(12), 2649; https://doi.org/10.3390/v14122649 - 27 Nov 2022
Cited by 1 | Viewed by 1331
Abstract
Lassa virus (LASV) is a highly pathogenic virus that is categorized as a biosafety level-4 pathogen. Currently, there are no approved drugs or vaccines specific to LASV. In this study, high-throughput screening of a fragment-based drug discovery library was performed against LASV entry [...] Read more.
Lassa virus (LASV) is a highly pathogenic virus that is categorized as a biosafety level-4 pathogen. Currently, there are no approved drugs or vaccines specific to LASV. In this study, high-throughput screening of a fragment-based drug discovery library was performed against LASV entry using a pseudotype virus bearing the LASV envelope glycoprotein complex (GPC). Two compounds, F1920 and F1965, were identified as LASV entry inhibitors that block GPC-mediated membrane fusion. Analysis of adaptive mutants demonstrated that the transient mutants L442F and I445S, as well as the constant mutant F446L, were located on the same side on the transmembrane domain of the subunit GP2 of GPC, and all the mutants conferred resistance to both F1920 and F1965. Furthermore, F1920 antiviral activity extended to other highly pathogenic mammarenaviruses, whereas F1965 was LASV-specific. Our study showed that both F1920 and F1965 provide a potential backbone for the development of lead drugs for preventing LASV infection. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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16 pages, 4027 KiB  
Article
Chemically Modified Bovine β-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks
by Yuhong Fu, Peiyu Li, Wei Xu, Zezhong Liu, Cong Wang, Qian Wang, Jiayi Tang, Weihua Li, Lu Lu and Shibo Jiang
Viruses 2022, 14(9), 2055; https://doi.org/10.3390/v14092055 - 16 Sep 2022
Cited by 1 | Viewed by 1962
Abstract
Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) [...] Read more.
Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human papillomavirus (HPV) infections. Here, we show its efficacy in potently inhibiting infection by divergent influenza A and B viruses. Mechanistic studies suggest that 3HP-β-LG binds, possibly through its negatively charged residues, to the receptor-binding domain in the hemagglutinin 1 (HA1) subunit in the HA of the influenza virus, thus inhibiting the attachment of the HA to sialic acid on host cells. The intranasal administration of 3HP-β-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-β-LG is highly stable when stored at 50 °C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-β-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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14 pages, 1782 KiB  
Article
Fusion Proteins CLD and CLDmut Demonstrate Potent and Broad Neutralizing Activity against HIV-1
by Ming Fu, Yingying Xiao, Tao Du, Huimin Hu, Fengfeng Ni, Kai Hu and Qinxue Hu
Viruses 2022, 14(7), 1365; https://doi.org/10.3390/v14071365 - 23 Jun 2022
Cited by 1 | Viewed by 1652
Abstract
HIV-1 envelope glycoprotein (Env) interacts with cellular receptors and mediates virus entry into target cells. Blocking Env-receptor interactions represents an effective interventional strategy for developing HIV-1 entry inhibitors. We previously designed a panel of CD4-linker-DC-SIGN (CLD) constructs by fusing the extracellular CD4 and [...] Read more.
HIV-1 envelope glycoprotein (Env) interacts with cellular receptors and mediates virus entry into target cells. Blocking Env-receptor interactions represents an effective interventional strategy for developing HIV-1 entry inhibitors. We previously designed a panel of CD4-linker-DC-SIGN (CLD) constructs by fusing the extracellular CD4 and DC-SIGN domains with various linkers. Such CLDs produced by the prokaryotic system efficiently inhibited HIV-1 infection and dissemination in vitro and ex vivo. In this study, following the construction and identification of the most promising candidate with a linker of 8 Gly4Ser repeats (named CLD), we further designed an improved form (named CLDmut) by back mutating Cys to Ser at amino acid 60 of CD4. Both CLD and CLDmut were produced in mammalian (293F) cells for better protein translation and modification. The anti-HIV-1 activity of CLD and CLDmut was assessed against the infection of a range of HIV-1 isolates, including transmitted and founder (T/F) viruses. While both CLD and CLDmut efficiently neutralized the tested HIV-1 isolates, CLDmut demonstrated much higher neutralizing activity than CLD, with an IC50 up to one log lower. The neutralizing activity of CLDmut was close to or more potent than those of the highly effective HIV-1 broadly neutralizing antibodies (bNAbs) reported to date. Findings in this study indicate that mammalian cell-expressed CLDmut may have the potential to be used as prophylaxis or/and therapeutics against HIV-1 infection. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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18 pages, 3233 KiB  
Article
Tyrosine 146 of the Human Na+/Taurocholate Cotransporting Polypeptide (NTCP) Is Essential for Its Hepatitis B Virus (HBV) Receptor Function and HBV Entry into Hepatocytes
by Dariusz Zakrzewicz, Regina Leidolf, Sebastian Kunz, Simon Franz Müller, Anita Neubauer, Silke Leiting, Nora Goldmann, Felix Lehmann, Dieter Glebe and Joachim Geyer
Viruses 2022, 14(6), 1259; https://doi.org/10.3390/v14061259 - 09 Jun 2022
Cited by 5 | Viewed by 2052
Abstract
Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) is a hepatic bile acid uptake carrier participating in the enterohepatic circulation of bile acids. Apart from its transporter function, NTCP acts as the high-affinity liver-specific receptor for the hepatitis B virus (HBV), which [...] Read more.
Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) is a hepatic bile acid uptake carrier participating in the enterohepatic circulation of bile acids. Apart from its transporter function, NTCP acts as the high-affinity liver-specific receptor for the hepatitis B virus (HBV), which attaches via its preS1-peptide domain of the large surface protein to NTCP, subsequently leading to endocytosis of the virus/NTCP-receptor complex. Although the process of NTCP-dependent HBV infection of hepatocytes has received much attention over the last decade, the precise molecular sites of the virus/NTCP interaction have not been fully identified. Inspection of the primary protein sequence of human NTCP revealed 139YIYSRGIY146 as a highly conserved tyrosine-rich motif. To study the role of Y139, Y141 and Y146 amino acids in NTCP biology, the aforementioned residues were substituted with alanine, phenylalanine or glutamate (mimicking phosphorylation) using site-directed mutagenesis. Similar to wt NTCP, the Y139A, Y141A, Y146A, Y141F, Y146F, and Y146E mutants were expressed at the plasma membrane of HEK293 cells and exhibited intact bile acid transport function. Y146A, Y146E, and Y146F demonstrated transport kinetics comparable to wild-type NTCP with Km values of 57.3–112.4 µM and Vmax values of 6683–7579 pmol/mg protein/min. Only Y141E was transport deficient, most likely due to an intracellular accumulation of the mutant protein. Most importantly, Y146A and Y146E mutation completely abrogated binding of the viral preS1-peptide to NTCP, while the Y146F mutant of NTCP showed some residual binding competence for preS1. Consequently, the NTCP mutants Y146A and Y146E, when expressed in HepG2 hepatoma cells, showed complete loss of susceptibility for in vitro HBV infection. In conclusion, tyrosine 146, and to some extent tyrosine 141, both belonging to the tyrosine-rich motif 139YIYSRGIY146 of human NTCP, are newly identified amino acid residues that play an essential role in the interaction of HBV with its receptor NTCP and, thus, in the process of virus entry into hepatocytes. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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17 pages, 3205 KiB  
Article
In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage
by E. Sila Ozdemir, Hillary H. Le, Adem Yildirim and Srivathsan V. Ranganathan
Viruses 2022, 14(6), 1129; https://doi.org/10.3390/v14061129 - 24 May 2022
Cited by 4 | Viewed by 1951
Abstract
The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting spike (S) [...] Read more.
The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting spike (S) protein cleavage by several proteases. We developed a computational pipeline to repurpose FDA-approved drugs to inhibit protease activity and thus prevent S protein cleavage. We tested some of our drug candidates and demonstrated a decrease in protease activity. We believe our pipeline will be beneficial in identifying a drug regimen for COVID-19 patients. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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16 pages, 3133 KiB  
Article
Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator
by Yongkang Chen, Xiaohuan Wang, Huichun Shi and Peng Zou
Viruses 2022, 14(5), 861; https://doi.org/10.3390/v14050861 - 21 Apr 2022
Cited by 5 | Viewed by 2519
Abstract
Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with [...] Read more.
Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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20 pages, 1673 KiB  
Article
IFITM3 Interacts with the HBV/HDV Receptor NTCP and Modulates Virus Entry and Infection
by Massimo Palatini, Simon Franz Müller, Michael Kirstgen, Silke Leiting, Felix Lehmann, Lena Soppa, Nora Goldmann, Christin Müller, Kira Alessandra Alicia Theresa Lowjaga, Jörg Alber, Giuliano Ciarimboli, John Ziebuhr, Dieter Glebe and Joachim Geyer
Viruses 2022, 14(4), 727; https://doi.org/10.3390/v14040727 - 30 Mar 2022
Cited by 8 | Viewed by 3490
Abstract
The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this [...] Read more.
The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this process is not fully understood. As part of the innate immunity, interferon-induced transmembrane proteins (IFITM) 1–3 have been characterized as virus entry-restricting factors for many viruses. The present study identified IFITM3 as a novel protein–protein interaction (PPI) partner of NTCP based on membrane yeast-two hybrid and co-immunoprecipitation experiments. Surprisingly, IFITM3 knockdown significantly reduced in vitro HBV infection rates of NTCP-expressing HuH7 cells and primary human hepatocytes (PHHs). In addition, HuH7-NTCP cells showed significantly lower HDV infection rates, whereas infection with influenza A virus was increased. HBV-derived myr-preS1 peptide binding to HuH7-NTCP cells was intact even under IFITM3 knockdown, suggesting that IFITM3-mediated HBV/HDV infection enhancement occurs in a step subsequent to the viral attachment to NTCP. In conclusion, IFITM3 was identified as a novel NTCP co-factor that significantly affects in vitro infection with HBV and HDV in NTCP-expressing hepatoma cells and PHHs. While there is clear evidence for a direct PPI between IFITM3 and NTCP, the specific mechanism by which this PPI facilitates the infection process remains to be identified in future studies. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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17 pages, 2331 KiB  
Article
A Modified Fibronectin Type III Domain-Conjugated, Long-Acting Pan-Coronavirus Fusion Inhibitor with Extended Half-Life
by Qianyu Duan, Shuai Xia, Fanke Jiao, Qian Wang, Rui Wang, Lu Lu, Shibo Jiang and Wei Xu
Viruses 2022, 14(4), 655; https://doi.org/10.3390/v14040655 - 22 Mar 2022
Cited by 7 | Viewed by 2306
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by infection of SARS-CoV-2 and its variants has posed serious threats to global public health, thus calling for the development of potent and broad-spectrum antivirals. We previously designed and developed a peptide-based pan-coronavirus (CoV) fusion inhibitor, [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic caused by infection of SARS-CoV-2 and its variants has posed serious threats to global public health, thus calling for the development of potent and broad-spectrum antivirals. We previously designed and developed a peptide-based pan-coronavirus (CoV) fusion inhibitor, EK1, which is effective against all human CoVs (HCoV) tested by targeting the HCoV S protein HR1 domain. However, its relatively short half-life may limit its clinical use. Therefore, we designed, constructed, and expressed a recombinant protein, FL-EK1, which consists of a modified fibronectin type III domain (FN3) with albumin-binding capacity, a flexible linker, and EK1. As with EK1, we found that FL-EK1 could also effectively inhibit infection of SARS-CoV-2 and its variants, as well as HCoV-OC43. Furthermore, it protected mice from infection by the SARS-CoV-2 Delta variant and HCoV-OC43. Importantly, the half-life of FL-EK1 (30 h) is about 15.7-fold longer than that of EK1 (1.8 h). These results suggest that FL-EK1 is a promising candidate for the development of a pan-CoV fusion inhibitor-based long-acting antiviral drug for preventing and treating infection by current and future SARS-CoV-2 variants, as well as other HCoVs. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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14 pages, 2592 KiB  
Article
A Five-Helix-Based SARS-CoV-2 Fusion Inhibitor Targeting Heptad Repeat 2 Domain against SARS-CoV-2 and Its Variants of Concern
by Lixiao Xing, Xinfeng Xu, Wei Xu, Zezhong Liu, Xin Shen, Jie Zhou, Ling Xu, Jing Pu, Chan Yang, Yuan Huang, Lu Lu, Shibo Jiang and Shuwen Liu
Viruses 2022, 14(3), 597; https://doi.org/10.3390/v14030597 - 13 Mar 2022
Cited by 22 | Viewed by 3907
Abstract
The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, [...] Read more.
The prolonged duration of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has resulted in the continuous emergence of variants of concern (VOC, e.g., Omicron) and variants of interest (VOI, e.g., Lambda). These variants have challenged the protective efficacy of current COVID-19 vaccines, thus calling for the development of novel therapeutics against SARS-CoV-2 and its VOCs. Here, we constructed a novel fusion inhibitor-based recombinant protein, denoted as 5-Helix, consisting of three heptad repeat 1 (HR1) and two heptad repeat 2 (HR2) fragments. The 5-Helix interacted with the HR2 domain of the viral S2 subunit, the most conserved region in spike (S) protein, to block homologous six-helix bundle (6-HB) formation between viral HR1 and HR2 domains and, hence, viral S-mediated cell–cell fusion. The 5-Helix potently inhibited infection by pseudotyped SARS-CoV-2 and its VOCs, including Delta and Omicron variants. The 5-Helix also inhibited infection by authentic SARS-CoV-2 wild-type (nCoV-SH01) strain and its Delta variant. Collectively, our findings suggest that 5-Helix can be further developed as either a therapeutic or prophylactic to treat and prevent infection by SARS-CoV-2 and its variants. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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11 pages, 2826 KiB  
Article
A Palmitic Acid-Conjugated, Peptide-Based pan-CoV Fusion Inhibitor Potently Inhibits Infection of SARS-CoV-2 Omicron and Other Variants of Concern
by Qiaoshuai Lan, Jasper Fuk-Woo Chan, Wei Xu, Lijue Wang, Fanke Jiao, Guangxu Zhang, Jing Pu, Jie Zhou, Shuai Xia, Lu Lu, Kwok-Yung Yuen, Shibo Jiang and Qian Wang
Viruses 2022, 14(3), 549; https://doi.org/10.3390/v14030549 - 06 Mar 2022
Cited by 12 | Viewed by 2688
Abstract
Our previous studies have shown that cholesterol-conjugated, peptide-based pan-coronavirus (CoV) fusion inhibitors can potently inhibit human CoV infection. However, only palmitic acid (C16)-based lipopeptide drugs have been tested clinically, suggesting that the development of C16-based lipopeptide drugs is feasible. Here, we designed and [...] Read more.
Our previous studies have shown that cholesterol-conjugated, peptide-based pan-coronavirus (CoV) fusion inhibitors can potently inhibit human CoV infection. However, only palmitic acid (C16)-based lipopeptide drugs have been tested clinically, suggesting that the development of C16-based lipopeptide drugs is feasible. Here, we designed and synthesized a C16-modified pan-CoV fusion inhibitor, EK1-C16, and found that it potently inhibited infection by SARS-CoV-2 and its variants of concern (VOCs), including Omicron, and other human CoVs and bat SARS-related CoVs (SARSr-CoVs). These results suggest that EK1-C16 could be further developed for clinical use to prevent and treat infection by the currently circulating MERS-CoV, SARS-CoV-2 and its VOCs, as well as any future emerging or re-emerging coronaviruses. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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13 pages, 3021 KiB  
Article
The Analogs of Furanyl Methylidene Rhodanine Exhibit Broad-Spectrum Inhibitory and Inactivating Activities against Enveloped Viruses, including SARS-CoV-2 and Its Variants
by Jing Pu, Xiaoyang He, Wei Xu, Cong Wang, Qiaoshuai Lan, Chen Hua, Kai Wang, Lu Lu and Shibo Jiang
Viruses 2022, 14(3), 489; https://doi.org/10.3390/v14030489 - 27 Feb 2022
Cited by 7 | Viewed by 2323
Abstract
In recent years, infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide. The development of broad-spectrum antiviral inhibitors is urgently needed. Here, we report a series of small-molecule compounds that proved [...] Read more.
In recent years, infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide. The development of broad-spectrum antiviral inhibitors is urgently needed. Here, we report a series of small-molecule compounds that proved effective against human coronaviruses (HCoV), such as SARS-CoV-2 and its variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), SARS-CoV, MERS-CoV, HCoV-OC43, and other viruses with class I viral fusion proteins, such as influenza virus, Ebola virus (EBOV), Nipah virus (NiV), and Lassa fever virus (LASV). They are also effective against class II enveloped viruses represented by ZIKV and class III enveloped viruses represented by vesicular stomatitis virus (VSV). Further studies have shown that these compounds may exert antiviral effects through a variety of mechanisms, including inhibiting the formation of the six-helix bundle, which is a typical feature of enveloped virus fusion with cell membranes, and/or targeting viral membrane to inactivate cell-free virions. These compounds are expected to become drug candidates against SARS-CoV-2 and other enveloped viruses. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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Review

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15 pages, 1513 KiB  
Review
Designed Ankyrin Repeat Proteins: A New Class of Viral Entry Inhibitors
by Marcel Walser, Jennifer Mayor and Sylvia Rothenberger
Viruses 2022, 14(10), 2242; https://doi.org/10.3390/v14102242 - 12 Oct 2022
Cited by 7 | Viewed by 1684
Abstract
Designed ankyrin repeat proteins (DARPins) are engineered proteins comprising consensus designed ankyrin repeats as scaffold. Tightly packed repeats form a continuous hydrophobic core and a large groove-like solvent-accessible surface that creates a binding surface. DARPin domains recognizing a target of interest with high [...] Read more.
Designed ankyrin repeat proteins (DARPins) are engineered proteins comprising consensus designed ankyrin repeats as scaffold. Tightly packed repeats form a continuous hydrophobic core and a large groove-like solvent-accessible surface that creates a binding surface. DARPin domains recognizing a target of interest with high specificity and affinity can be generated using a synthetic combinatorial library and in vitro selection methods. They can be linked together in a single molecule to build multispecific and multifunctional proteins without affecting expression or function. The modular architecture of DARPins offers unprecedented possibilities of design and opens avenues for innovative antiviral strategies. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2022)
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