In Silico Discovery of a Novel Antiviral Scaffold for SARS-CoV-2 Targeting the Spike Glycoprotein through the Fatty Acid Binding Pocket
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F25%3A43932945" target="_blank" >RIV/60461373:22310/25:43932945 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsomega.4c10519" target="_blank" >https://pubs.acs.org/doi/10.1021/acsomega.4c10519</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsomega.4c10519" target="_blank" >10.1021/acsomega.4c10519</a>
Alternative languages
Result language
angličtina
Original language name
In Silico Discovery of a Novel Antiviral Scaffold for SARS-CoV-2 Targeting the Spike Glycoprotein through the Fatty Acid Binding Pocket
Original language description
The key viral protein for infection by SARS-CoV-2 is the spike glycoprotein (S protein), mediating entry into host cells, which therefore represents a strong focus for the development of targeted therapeutics. In this work, we explored the fatty acid binding pocket within the S protein, which stabilizes an inactive conformation and disrupts cell recognition and infection. To explore the potential of this site as a drug target, molecular dynamics simulations were performed, followed by a docking-based virtual screening of commercial druglike compounds. This in silico procedure enabled the identification of potential inhibitors of SARS-CoV-2 cell infection, likely by stabilizing an inactive spike conformation, detected in binding assays, although further experiments are required to directly confirm this action. The antiviral effect of the virtual hits was analyzed in cell-based assays, and one molecule displayed a low micromolar activity. Starting from the best antiviral compound found, structural analogues were purchased and evaluated in antiviral assays. An increase in activity was observed for multiple analogues, with the strongest antiviral compound showing submicromolar activity and low cytotoxicity. The successful identification of a new antiviral scaffold through in silico studies might pave the way for the further development of antivirals against SARS-CoV-2 and shows the reliability of the methodologies applied.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Omega
ISSN
2470-1343
e-ISSN
2470-1343
Volume of the periodical
10
Issue of the periodical within the volume
23
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
24117-24132
UT code for WoS article
001502891200001
EID of the result in the Scopus database
2-s2.0-105007501282