Innovative Drug Discovery for Emerging Viral Diseases

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 800

Special Issue Editors


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Guest Editor
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA
Interests: HIV-1 protease autoprocessing mechanism and drug discovery

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Guest Editor
Aligos Therapeutics, Inc., South San Francisco, CA 94080, USA
Interests: antiviral drug discovery; HBV; SARS-CoV-2

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has highlighted the sobering potential of certain members of several viral families to cause unexpected outbreaks with high-burden diseases that might disrupt healthcare systems and devastate economies in the future. Currently, no highly active direct-acting antiviral drugs are available for several virus families such as the togaviridae (chikungunya virus), hantaviridae (Hantavirus) or the filoviridae (Ebolavirus, Marburg Virus). Additionally, the rapid development of drug resistance, exemplified by all classes of HIV antiretrovirals, presents extra hurdles to disease control. Therefore, proactive and innovative antiviral drug discovery is urgently needed to ensure preparedness to mitigate the threat caused by these viral pathogens.

Antivirals have traditionally been developed by directly targeting essential viral components through structure-based rational design. Other strategies have been less exploited, such as function-based high-throughput screening (HTS) either in vitro/vivo or in silicon, targeting host factors that are critical for virus replication but dispensable for the host, and potentiation of immune responses (i.e., immunomodulators). This Special Issue of Viruses seeks to attract top-level publications covering conventional or innovative designs, developments and validations of antivirals in relation to emerging/re-emerging RNA viral pathogens. We invite you to share your most insightful research, reviews and hypotheses on these important topics.

Dr. Chaoping Chen
Dr. Andreas Jekle
Guest Editors

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.

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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

  • antivirals
  • drug discovery
  • high-throughput screen
  • SARS-CoV-2
  • Influenza virus
  • RSV
  • Zika
  • Ebola Virus
  • chikungunya virus
  • emerging/re-emerging RNA viral pathogens
  • host-directed therapies
  • immunomodulator

Published Papers (1 paper)

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Research

21 pages, 7637 KiB  
Article
The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein
by Matthew R. Freidel, Pratiti A. Vakhariya, Shalinder K. Sardarni and Roger S. Armen
Viruses 2024, 16(4), 640; https://doi.org/10.3390/v16040640 - 20 Apr 2024
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Abstract
Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed [...] Read more.
Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results related to molecular docking and modeling of the structure–activity relationship (SAR) of a newly reported series of Clofazimine derivatives support the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure–sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronaviruses such as SARS-CoV, MERS, hCoV-229E, and hCoV-OC43. Full article
(This article belongs to the Special Issue Innovative Drug Discovery for Emerging Viral Diseases)
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