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Biomolecules
Special Issues
Molecular Virology: Mechanisms of Viral Entry and Antivirals
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Molecular Virology: Mechanisms of Viral Entry and Antivirals

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 4213

Special Issue Editors

Prof. Dr. Lijun Rong

E-Mail Website
Guest Editor
College of Medicine, University of Illinois, Chicago, IL, USA
Interests: studying entry and replication mechanisms of viruses with pandemic potential, and developing antivirals
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Lu Lu

E-Mail Website
Guest Editor
Key Laboratory of Medical Molecular Virology of Ministries of Health and Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
Interests: antivirals; mechanisms of viral entry; entry inhibitors; peptide inhibitors; vaccine; coronavirus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our Special Issue, “Molecular Virology: Mechanisms of Viral Entry and Antivirals”. Recent advances in molecular virology have broadened our understanding of the pathogenic mechanisms of many viruses and strategies for controlling them. For instance, viral entry into the target cell is the earliest step, and a crucial one, in the life cycle of a virus. This is a complicated multi-step process that is initiated by attachment to receptors and ends with the transfer of viral genomes inside host cells. This process involves diverse viral and host proteins, which have been identified as important targets for vaccine and drug development. Besides viral entry, studies of antivirals often focus on other viral molecules such as protease, polymerase and integrase, or on host cell factors.

This Special Issue aims to provide an advanced forum for molecular virology studies focusing on the mechanisms of viral entry and antivirals. The viruses of interest include (but are not limited to) SARS-CoV-2, monkeypox viruses, influenza viruses and HIV-1. We hope that this Special Issue will provide further insight into the viral entry mechanism, as well as the mechanisms of action of antiviral agents and vaccines.

We look forward to receiving your contributions.

Prof. Dr. Lijun Rong
Prof. Dr. Lu Lu
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.

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. Biomolecules 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 2700 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

  • viral entry
  • entry inhibitor
  • antivirals
  • SARS-CoV-2
  • monkeypox
  • flu
  • HIV
  • broad-spectrum inhibitor

Published Papers (3 papers)

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Research

15 pages, 3986 KiB  
Article
Antiviral Functions of Type I and Type III Interferons in the Olfactory Epithelium
by Ahmad Zedan, Ashley D. Winters, Wei Yu, Shuangyan Wang, Ying Ren, Ashley Takeshita and Qizhi Gong
Biomolecules 2023, 13(12), 1762; https://doi.org/10.3390/biom13121762 - 08 Dec 2023
Cited by 1 | Viewed by 922
Abstract
The olfactory neuroepithelium (OE) is one of the few neuronal tissues where environmental pathogens can gain direct access. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and its antiviral responses. We systematically investigated [...] Read more.
The olfactory neuroepithelium (OE) is one of the few neuronal tissues where environmental pathogens can gain direct access. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and its antiviral responses. We systematically investigated acute responses in the olfactory mucosa upon exposure to vesicular stomatitis virus (VSV) via RNA-seq. VSVs were nasally inoculated into C57BL/6 mice. Olfactory mucosae were dissected for gene expression analysis at different time points after viral inoculation. Interferon functions were determined by comparing the viral load in interferon receptor knockout (Ifnar1−/− and Ifnlr1−/−) with wildtype OE. Antiviral responses were observed as early as 24 h after viral exposure in the olfactory mucosa. The rapidly upregulated transcripts observed included specific type I as well as type III interferons (Ifn) and interferon-stimulated genes. Genetic analyses demonstrated that both type I and type III IFN signaling are required for the suppression of viral replication in the olfactory mucosa. Exogenous IFN application effectively blocks viral replication in the OE. These findings reveal that the OE possesses an innate ability to suppress viral infection. Type I and type III IFNs have prominent roles in OE antiviral functions. Full article
(This article belongs to the Special Issue Molecular Virology: Mechanisms of Viral Entry and Antivirals)
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19 pages, 2991 KiB  
Article
cccDNA-Targeted Drug Screen Reveals a Class of Antihistamines as Suppressors of HBV Genome Levels
by Ee Chee Ren, Nicole Ziyi Zhuo, Zhi Yi Goh, Isabelle Bonne, Benoît Malleret and Hui Ling Ko
Biomolecules 2023, 13(10), 1438; https://doi.org/10.3390/biom13101438 - 24 Sep 2023
Viewed by 1356
Abstract
Chronic infection with hepatitis B virus (HBV) is incurable, as the current therapeutics cannot eliminate its persistent genomic material, cccDNA. Screening systems for cccDNA-targeting therapeutics are unavailable, as low copies of cccDNA in vitro complicate detection. To address this, cccDNA copies were massively [...] Read more.
Chronic infection with hepatitis B virus (HBV) is incurable, as the current therapeutics cannot eliminate its persistent genomic material, cccDNA. Screening systems for cccDNA-targeting therapeutics are unavailable, as low copies of cccDNA in vitro complicate detection. To address this, cccDNA copies were massively increased to levels detectable via automated plate readers. This was achieved via continuous infection in a contact-free co-culture of an HBV generator (clone F881), which stably produced clinically relevant amounts of HBV, and HBV acceptors selected to carry high cccDNA loads. cccDNA-targeted therapeutics were then identified via reduced cccDNA-specific fluorescence, taking differences in the cell numbers and viability into account. Amongst the drugs tested, the H1 antihistamine Bilastine, HBVCP inhibitors and, surprisingly, current HBV therapeutics downregulated the cccDNA significantly, reflecting the assay’s accuracy and sensitivity in identifying drugs that induce subtle changes in cccDNA levels, which take years to manifest in vivo. Bilastine was the only therapeutic that did not reduce HBV production from F881, indicating it to be a novel direct suppressor of cccDNA levels. When further assessed, only the structurally similar antihistamines Pitolisant and Nizatidine suppressed cccDNA levels when other H1 antihistamines could not. Taken together, our rapid fluorescence cccDNA-targeted drug screen successfully identified a class of molecules with the potential to treat hepatitis B. Full article
(This article belongs to the Special Issue Molecular Virology: Mechanisms of Viral Entry and Antivirals)
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27 pages, 4899 KiB  
Article
IgG Fc-Binding Peptide-Conjugated Pan-CoV Fusion Inhibitor Exhibits Extended In Vivo Half-Life and Synergistic Antiviral Effect When Combined with Neutralizing Antibodies
by Xiaojie Su, Ziqi Huang, Wei Xu, Qian Wang, Lixiao Xing, Lu Lu, Shibo Jiang and Shuai Xia
Biomolecules 2023, 13(9), 1283; https://doi.org/10.3390/biom13091283 - 22 Aug 2023
Viewed by 1374
Abstract
The peptide-based pan-coronavirus fusion inhibitor EK1 is in phase III clinical trials, and it has, thus far, shown good clinical application prospects against SARS-CoV-2 and its variants. To further improve its in vivo long-acting property, we herein developed an Fc-binding strategy by conjugating [...] Read more.
The peptide-based pan-coronavirus fusion inhibitor EK1 is in phase III clinical trials, and it has, thus far, shown good clinical application prospects against SARS-CoV-2 and its variants. To further improve its in vivo long-acting property, we herein developed an Fc-binding strategy by conjugating EK1 with human immunoglobulin G Fc-binding peptide (IBP), which can exploit the long half-life advantage of IgG in vivo. The newly engineered peptide IBP-EK1 showed potent and broad-spectrum inhibitory activity against SARS-CoV-2 and its variants, including various Omicron sublineages and other human coronaviruses (HCoVs) with low cytotoxicity. In mouse models, IBP-EK1 possessed potent prophylactic and therapeutic efficacy against lethal HCoV-OC43 challenge, and it showed good safety profile and low immunogenicity. More importantly, IBP-EK1 exhibited a significantly extended in vivo half-life in rhesus monkeys of up to 37.7 h, which is about 20-fold longer than that reported for EK1. Strikingly, IBP-EK1 displayed strong in vitro or ex vivo synergistic anti-HCoV effect when combined with monoclonal neutralizing antibodies, including REGN10933 or S309, suggesting that IBP-conjugated EK1 can be further developed as a long-acting, broad-spectrum anti-HCoV agent, either alone or in combination with neutralizing antibodies, to combat the current COVID-19 pandemic or future outbreaks caused by emerging and re-emerging highly pathogenic HCoVs. Full article
(This article belongs to the Special Issue Molecular Virology: Mechanisms of Viral Entry and Antivirals)
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