Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Virus Entry Inhibitors
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Virus Entry Inhibitors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Informatics".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 2394

Special Issue Editor

Dr. Asim Debnath

E-Mail Website
Guest Editor
Laboratory of Molecular Modeling and Drug Design, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
Interests: rational design of antiviral drugs, e.g., virus entry/fusion inhibitors, protease inhibitors, etc.; computer-assisted drug design; structure-based drug design; ligand-based drug design; virtual screening; QSAR; 3D-QSAR; pharmacophore mapping
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to inform you of the launch of a Special Issue on “Virus Entry Inhibitors” in IJMS. Virus entry into host cells is the first step of all enveloped and non-enveloped viruses. Virus entry inhibitors are a class of antiviral drugs that prevent the entry or fusion of a virus into a host cell. These inhibitors target specific mechanisms or proteins involved in the virus entry process, thereby blocking the virus from infecting the host cell.

Considerable progress has been made in this area of research, especially since the FDA approved the first HIV-1 fusion inhibitor, enfuvirtide (brand name Fuzeon), and CCR5 antagonist maraviroc (brand name Selzentry).

With this Special Issue, we will aim to provide an overview of the latest progress in the development of entry inhibitors that include small molecules, peptidomimetics, and that are peptide-based or antibody-based (such as broadly neutralizing antibody (bNAb), etc. We also want to encourage the submission of novel findings on virus entry mechanisms, preclinical and clinical assessments of virus entry inhibitors, and the future trends in developing these inhibitors.

We encourage the submission of original research articles, brief communications, reviews, and commentaries. We look forward to receiving your contributions.

Dr. Asim Debnath
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 inhibitors
  • small molecules
  • peptidomimetics
  • peptide-based
  • broadly neutralizing antibody (bNAb)

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

14 pages, 2923 KiB  
Article
Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection
by Li-Te Tai, Cheng-Yun Yeh, Yu-Jen Chang, Ju-Fang Liu, Kai-Cheng Hsu, Ju-Chien Cheng and Chih-Hao Lu
Int. J. Mol. Sci. 2024, 25(11), 6105; https://doi.org/10.3390/ijms25116105 - 1 Jun 2024
Viewed by 669
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor [...] Read more.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein–ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC50 values of 8.8 μM, 6.7 μM, and 7.6 μM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC50 = 5.9 μM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC50 of 9.3 μM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection. Full article
(This article belongs to the Special Issue Virus Entry Inhibitors)
►▼ Show Figures

Graphical abstract

15 pages, 5186 KiB  
Article
Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres
by Patrick Müller, Collin Zimmer, Ariane Frey, Gideon Holzmann, Annabelle Carolin Weldert and Tanja Schirmeister
Int. J. Mol. Sci. 2024, 25(3), 1375; https://doi.org/10.3390/ijms25031375 - 23 Jan 2024
Viewed by 1122
Abstract
Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the [...] Read more.
Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the metastatic behavior of various cancer types when overexpressed and dysregulated. Another member of this protease class that received attention during the SARS-CoV 2 pandemic is TMPRSS2. It is a transmembrane serine protease, which enables cell entry of the coronavirus by processing its spike protein. A variety of different inhibitors have been published against both proteases. However, the selectivity over other trypsin-like serine proteases remains a major challenge. In the current study, we replaced the arginine moiety at the P1 site of peptidomimetic inhibitors with different bioisosteres. Enzyme inhibition studies revealed that the phenylguanidine moiety in the P1 site led to strong affinity for TMPRSS2, whereas the cyclohexylguanidine derivate potently inhibited uPA. Both inhibitors exhibited high selectivity over other structurally similar and physiologically important proteases. Full article
(This article belongs to the Special Issue Virus Entry Inhibitors)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop