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Viruses
Special Issues
Strategies for the Discovery of Antivirals against Respiratory RNA Viruses
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Strategies for the Discovery of Antivirals against Respiratory RNA Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 26779

Special Issue Editor

Dr. Meehyein Kim

E-Mail
Guest Editor
Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, Korea
Interests: influenza virus; SARS-CoV; MERS-CoV; antiviral; innate immune response; viral RNA replication

Special Issue Information

Dear Colleagues,

Emerging and re-emerging respiratory RNA viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and G4 swine influenza virus, have become a great threat to global public health. With the exception of influenza A and B viruses and respiratory syncytial virus (RSV), there are no FDA-approved, virus-specific drugs for the treatment of infections with other human respiratory viruses, such as coronaviruses, rhinoviruses, and parainfluenza viruses. Even though influenza viruses have a relatively diverse range of treatment options due to the long-term development of strategies for direct-acting antivirals, the rapid and sporadic generation of genetic mutations has resulted in the circulation of drug-resistant strains. RSV can be treated with an aerosolized antiviral or prevented by a neutralizing antibody; however, there remain limitations to the antiviral drug in terms of specificity and cost-effectiveness.

There is an urgent need for the development of novel antivirals and the identification of drug targets derived from either viral proteins or host factors, by which therapeutic effects could be induced efficiently and sufficiently. This Special Issue focuses on recent progress in antiviral discovery, investigation of the mode-of-action, target validation, and establishment of drug screening methods. We hope that this Special Issue will allow researchers to share scientific insights to help find a therapeutic way to treat human respiratory virus infection-mediated diseases in the ongoing pandemic situation or in order to be prepared for possible upcoming pandemics.

Dr. Meehyein Kim
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • influenza virus
  • SARS-CoV-2
  • respiratory viruses
  • antivirals
  • target validation

Related Special Issue

Published Papers (5 papers)

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Research

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12 pages, 4672 KiB  
Communication
The Impact on Infectivity and Neutralization Efficiency of SARS-CoV-2 Lineage B.1.351 Pseudovirus
by Yeong Jun Kim, Ui Soon Jang, Sandrine M. Soh, Joo-Youn Lee and Hye-Ra Lee
Viruses 2021, 13(4), 633; https://doi.org/10.3390/v13040633 - 07 Apr 2021
Cited by 39 | Viewed by 3982
Abstract
A new variant of SARS-CoV-2 B.1.351 lineage (first found in South Africa) has been raising global concern due to its harboring of multiple mutations in the spike that potentially increase transmissibility and yield resistance to neutralizing antibodies. We here tested infectivity and neutralization [...] Read more.
A new variant of SARS-CoV-2 B.1.351 lineage (first found in South Africa) has been raising global concern due to its harboring of multiple mutations in the spike that potentially increase transmissibility and yield resistance to neutralizing antibodies. We here tested infectivity and neutralization efficiency of SARS-CoV-2 spike pseudoviruses bearing particular mutations of the receptor-binding domain (RBD) derived either from the Wuhan strains (referred to as D614G or with other sites) or the B.1.351 lineage (referred to as N501Y, K417N, and E484K). The three different pseudoviruses B.1.351 lineage related significantly increased infectivity compared with other mutants that indicated Wuhan strains. Interestingly, K417N and E484K mutations dramatically enhanced cell–cell fusion than N501Y even though their infectivity were similar, suggesting that K417N and E484K mutations harboring SARS-CoV-2 variant might be more transmissible than N501Y mutation containing SARS-CoV-2 variant. We also investigated the efficacy of two different monoclonal antibodies, Casirivimab and Imdevimab that neutralized SARS-CoV-2, against several kinds of pseudoviruses which indicated Wuhan or B.1.351 lineage. Remarkably, Imdevimab effectively neutralized B.1.351 lineage pseudoviruses containing N501Y, K417N, and E484K mutations, while Casirivimab partially affected them. Overall, our results underscore the importance of B.1.351 lineage SARS-CoV-2 in the viral spread and its implication for antibody efficacy. Full article
(This article belongs to the Special Issue Strategies for the Discovery of Antivirals against Respiratory RNA Viruses)
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13 pages, 16424 KiB  
Article
Deep Transfer Learning Approach for Automatic Recognition of Drug Toxicity and Inhibition of SARS-CoV-2
by Julia Werner, Raphael M. Kronberg, Pawel Stachura, Philipp N. Ostermann, Lisa Müller, Heiner Schaal, Sanil Bhatia, Jakob N. Kather, Arndt Borkhardt, Aleksandra A. Pandyra, Karl S. Lang and Philipp A. Lang
Viruses 2021, 13(4), 610; https://doi.org/10.3390/v13040610 - 02 Apr 2021
Cited by 9 | Viewed by 3324
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 and is responsible for the ongoing pandemic. Screening of potential antiviral drugs against SARS-CoV-2 depend on in vitro experiments, which are based on the quantification of the virus titer. Here, we used virus-induced cytopathic effects [...] Read more.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 and is responsible for the ongoing pandemic. Screening of potential antiviral drugs against SARS-CoV-2 depend on in vitro experiments, which are based on the quantification of the virus titer. Here, we used virus-induced cytopathic effects (CPE) in brightfield microscopy of SARS-CoV-2-infected monolayers to quantify the virus titer. Images were classified using deep transfer learning (DTL) that fine-tune the last layers of a pre-trained Resnet18 (ImageNet). To exclude toxic concentrations of potential drugs, the network was expanded to include a toxic score (TOX) that detected cell death (CPETOXnet). With this analytic tool, the inhibitory effects of chloroquine, hydroxychloroquine, remdesivir, and emetine were validated. Taken together we developed a simple method and provided open access implementation to quantify SARS-CoV-2 titers and drug toxicity in experimental settings, which may be adaptable to assays with other viruses. The quantification of virus titers from brightfield images could accelerate the experimental approach for antiviral testing. Full article
(This article belongs to the Special Issue Strategies for the Discovery of Antivirals against Respiratory RNA Viruses)
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18 pages, 2439 KiB  
Article
In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2
by Jiongjiong Wang, Richard A. Prinz, Xiufan Liu and Xiulong Xu
Viruses 2020, 12(10), 1141; https://doi.org/10.3390/v12101141 - 08 Oct 2020
Cited by 23 | Viewed by 3434
Abstract
Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation “storms” in [...] Read more.
Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation “storms” in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections. Full article
(This article belongs to the Special Issue Strategies for the Discovery of Antivirals against Respiratory RNA Viruses)
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Review

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20 pages, 53904 KiB  
Review
Conserved Targets to Prevent Emerging Coronaviruses
by Fernanda Gonzalez Lomeli, Nicole Elmaraghy, Anthony Castro, Claudia V. Osuna Guerrero and Laura L. Newcomb
Viruses 2022, 14(3), 563; https://doi.org/10.3390/v14030563 - 09 Mar 2022
Cited by 2 | Viewed by 4827
Abstract
Novel coronaviruses emerged as zoonotic outbreaks in humans in 2003 (SARS), 2012 (MERS), and notably in 2019 (SARS2), which resulted in the COVID-19 pandemic, causing worldwide health and economic disaster. Vaccines provide the best protection against disease but cannot be developed and engineered [...] Read more.
Novel coronaviruses emerged as zoonotic outbreaks in humans in 2003 (SARS), 2012 (MERS), and notably in 2019 (SARS2), which resulted in the COVID-19 pandemic, causing worldwide health and economic disaster. Vaccines provide the best protection against disease but cannot be developed and engineered quickly enough to prevent emerging viruses, zoonotic outbreaks, and pandemics. Antivirals are the best first line of therapeutic defense against novel emerging viruses. Coronaviruses are plus sense, single stranded, RNA genome viruses that undergo frequent genetic mutation and recombination, allowing for the emergence of novel coronavirus strains and variants. The molecular life cycle of the coronavirus family offers many conserved activities to be exploited as targets for antivirals. Here, we review the molecular life cycle of coronaviruses and consider antiviral therapies, approved and under development, that target the conserved activities of coronaviruses. To identify additional targets to inhibit emerging coronaviruses, we carried out in silico sequence and structure analysis of coronavirus proteins isolated from bat and human hosts. We highlight conserved and accessible viral protein domains and residues as possible targets for the development of viral inhibitors. Devising multiple antiviral therapies that target conserved viral features to be used in combination is the best first line of therapeutic defense to prevent emerging viruses from developing into outbreaks and pandemics. Full article
(This article belongs to the Special Issue Strategies for the Discovery of Antivirals against Respiratory RNA Viruses)
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Other

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6 pages, 2475 KiB  
Perspective
Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset—Lessons Learned
by Lars Dölken, August Stich and Christoph D. Spinner
Viruses 2021, 13(6), 963; https://doi.org/10.3390/v13060963 - 22 May 2021
Cited by 12 | Viewed by 10131
Abstract
After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence [...] Read more.
After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence for the clinical efficacy of remdesivir in the right clinical settings, major trials failed to demonstrate this. Here, we highlight and discuss the key findings of these studies and underlying reasons for their failure. We elaborate on how such shortcomings should be prevented in future clinical trials and pandemics. We suggest in conclusion that any novel antiviral agent that enters human trials should first be tested in a post-exposure setting to provide rapid and solid evidence for its clinical efficacy before initiating further time-consuming and costly clinical trials for more advanced disease. In the COVID-19 pandemic this might have established remdesivir early on as an efficient antiviral agent at a more suitable disease stage which would have saved many lives, in particular in large outbreaks within residential care homes. Full article
(This article belongs to the Special Issue Strategies for the Discovery of Antivirals against Respiratory RNA Viruses)
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