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Potential SARS-CoV-2 protease Mpro inhibitors: repurposing FDA-approved drugs.

Authors
  • Kouznetsova, Valentina L1
  • Huang, David Z2
  • Tsigelny, Igor F1, 3
  • 1 San Diego Supercomputer Center, UC San Diego, California, Unites States of America.
  • 2 REHS program, San Diego Supercomputer Center, UC San Diego, California, Unites States of America.
  • 3 Dept. of Neurosciences, UC San Diego, California, Unites States of America.
Type
Published Article
Journal
Physical Biology
Publisher
IOP Publishing
Publication Date
Feb 09, 2021
Volume
18
Issue
2
Pages
25001–25001
Identifiers
DOI: 10.1088/1478-3975/abcb66
PMID: 33203811
Source
Medline
Language
English
License
Unknown

Abstract

Using as a template the crystal structure of the SARS-CoV-2 main protease, we developed a pharmacophore model of functional centers of the protease inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search brought 64 compounds that can be potential inhibitors of the SARS-CoV-2 protease. The conformations of these compounds undergone 3D fingerprint similarity clusterization. Then we conducted docking of possible conformers of these drugs to the binding pocket of the protease. We also conducted the same docking of random compounds. Free energies of the docking interaction for the selected compounds were clearly lower than random compounds. Three of the selected compounds were carfilzomib, cyclosporine A, and azithromycin-the drugs that already are tested for COVID-19 treatment. Among the selected compounds are two HIV protease inhibitors and two hepatitis C protease inhibitors. We recommend testing of the selected compounds for treatment of COVID-19.

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