Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2

Mohammad M. Ghahremanpour, Julian Tirado-Rives, Maya Deshmukh, Joseph A. Ippolito, Chun-Hui Zhang, Israel Cabeza de Vaca, Maria-Elena Liosi, Karen S. Anderson, William L. Jorgensen

10.1101/2020.08.28.271957

Research curated

Abstract

A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with Mpro, 17 were chosen for evaluation in a kinetic assay for Mpro inhibition. Remarkably 14 of the compounds at 100-μM concentration were found to reduce the enzymatic activity and 5 provided IC50 values below 40 μM: manidipine (4.8 μM), boceprevir (5.4 μM), lercanidipine (16.2 μM), bedaquiline (18.7 μM), and efonidipine (38.5 μM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1’, and P2 pockets of Mpro. Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.

Source: BioRxiv

Related molecules

Name	Synonyms	Genes
Bedaquiline
Carindacillin
Efonidipine
Idarubicin
Metergoline
Perampanel
Periciazine
Talampicillin
Dihydroergocristine
Boceprevir	Victrelis
Azelastine
Lapatinib
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Indinavir

Related interactions

Target	Drug	Type	Result
3C-like protease	Azelastine	Computational	positive
3C-like protease	Bedaquiline	Computational	positive
3C-like protease	Carindacillin	Computational	positive
3C-like protease	Dihydroergocristine	Computational	positive
3C-like protease	Efonidipine	Computational	positive
3C-like protease	Idarubicin	Computational	positive
3C-like protease	Lapatinib	Computational	positive
3C-like protease	Metergoline	Computational	positive
3C-like protease	Periciazine	Computational	positive
3C-like protease	Talampicillin	Computational	positive
3C-like protease	Boceprevir	Computational	positive
3C-like protease	Indinavir	Computational	positive
3C-like protease	Perampanel	Computational	positive