PT  - JOURNAL ARTICLE
AU  - Mohammad M. Ghahremanpour
AU  - Julian Tirado-Rives
AU  - Maya Deshmukh
AU  - Joseph A. Ippolito
AU  - Chun-Hui Zhang
AU  - Israel Cabeza de Vaca
AU  - Maria-Elena Liosi
AU  - Karen S. Anderson
AU  - William L. Jorgensen
TI  - Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2
AID  - 10.1101/2020.08.28.271957
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.28.271957
4099  - http://biorxiv.org/content/early/2020/08/28/2020.08.28.271957.short
4100  - http://biorxiv.org/content/early/2020/08/28/2020.08.28.271957.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.