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Viruses
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Viral Entry Inhibitors 2023
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Viral Entry Inhibitors 2023

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 November 2023) | Viewed by 5280

Special Issue Editor

Prof. Dr. Yuxian He

E-Mail Website
Guest Editor
Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Interests: HIV; SARS-CoV-2; antivirals; membrane fusion; fusion inhibitors; neutralizing antibodies; gene therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There are no effective antiviral drugs available for many viral infections, including emerging and re-emerging viruses that are constant threats to human health and wellbeing. Different from other classes of antivirals that act after the virus enters target cells, viral entry inhibitors block the first step in the viral life cycle and have unique advantages in suppressing viral infections, thus being of particular interest because of their potential to be used as therapeutic or prophylactic treatments. As exemplified by several clinically approved anti-HIV drugs, developing strategies of viral entry inhibitors are focused on two different approaches: targeting the viruses themselves or the host cell factors. The peptide-based drug Enfuvirtide is a membrane fusion inhibitor targeting the HIV-1 envelope glycoprotein gp41; Maraviroc is a small-molecule antagonist of the cell coreceptor CCR5; Ibalizumab is a humanized monoclonal antibody that binds to the receptor CD4; and Fostemsavir is an attachment inhibitor targeting the envelope glycoprotein gp120. The continued HIV/AIDS epidemic worldwide and the battle against the emerging SARS-CoV-2 underscore the need for the development of antiviral drugs with different mechanisms. In this Special Issue, we will appreciate the contributions from the studies on the mechanism of viral cell entry and inhibitors that especially block the entry step.

Prof. Dr. Yuxian He
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

  • antiviral drugs
  • viral entry
  • entry inhibitors
  • small-molecules
  • peptides
  • proteins
  • antibodies
  • HIV
  • SARS-CoV-2

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Published Papers (2 papers)

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12 pages, 3842 KiB  
Article
Susceptibility and Resistance of SARS-CoV-2 Variants to LCB1 and Its Multivalent Derivatives
by Hongliang Jin, Yani Gong, Lin Cheng, Yuanmei Zhu, Zheng Zhang and Yuxian He
Viruses 2024, 16(1), 36; https://doi.org/10.3390/v16010036 - 25 Dec 2023
Viewed by 1775
Abstract
LCB1 is a computationally designed three-helix miniprotein that precisely targets the spike (S) receptor-binding motif (RBM) of SARS-CoV-2, exhibiting remarkable antiviral efficacy; however, emerging SARS-CoV-2 variants could substantially compromise its neutralization effectiveness. In this study, we constructed two multivalent LCB1 fusion proteins termed [...] Read more.
LCB1 is a computationally designed three-helix miniprotein that precisely targets the spike (S) receptor-binding motif (RBM) of SARS-CoV-2, exhibiting remarkable antiviral efficacy; however, emerging SARS-CoV-2 variants could substantially compromise its neutralization effectiveness. In this study, we constructed two multivalent LCB1 fusion proteins termed LCB1T and LCB1T-Fc, and characterized their potency in inhibiting SARS-CoV-2 pseudovirus and authentic virus in vitro. In the inhibition of various SARS-CoV-2 variants, the two LCB1 fusion proteins exhibited markedly improved inhibitory activities compared to LCB1 as anticipated; however, it was observed that relative to the D614G mutation hosting variant, the variants Delta, Lambda, and Omicron BQ.1.1, XBB, XBB.1.5, and EG.5.1 caused various degrees of resistance to the two fusion proteins’ inhibition, with XBB, XBB.1.5, and EG.5.1 variants showing high-level resistance. Moreover, we demonstrated that bat coronavirus RaTG13 and pangolin coronavirus PCoV-GD/PCoV-GX were highly sensitive to two LCB1 fusion proteins, but not LCB1, inhibition. Importantly, our findings revealed a notable decrease in the blocking capacity of the multivalent LCB1 inhibitor on the interaction between the virus’s RBD/S and the cell receptor ACE2 when confronted with the XBB variant compared to WT and the Omicron BA.1 variant. In conclusion, our studies provide valuable insights into the antiviral profiling of multivalent LCB1 inhibitors and offer a promising avenue for the development of novel broad-spectrum antiviral therapeutics. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2023)
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Review

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15 pages, 4992 KiB  
Review
Causes and Consequences of Coronavirus Spike Protein Variability
by Fabian Zech, Christoph Jung, Timo Jacob and Frank Kirchhoff
Viruses 2024, 16(2), 177; https://doi.org/10.3390/v16020177 - 25 Jan 2024
Viewed by 2758
Abstract
Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven [...] Read more.
Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines. Full article
(This article belongs to the Special Issue Viral Entry Inhibitors 2023)
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