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

Valentina Kouznetsova, David Huang, Igor F. Tsigelny

10.1088/1478-3975/abcb66

Research curated

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.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Azithromycin	homoerythromycin A, Azithramycine, Azithromycin (TN), Azasite (TN), Azithromycin (INN)
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Carfilzomib
Ciclosporin	cyclosporine, cyclosporin, cyclosporine A

Related interactions

Target	Drug	Type	Result
3C-like protease	Azithromycin	Computational	positive
3C-like protease	Ciclosporin	Computational	positive
3C-like protease	Carfilzomib	Computational	positive