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Identification of Potential Inhibitors of SARS-CoV-2 Main Protease via a Rapid In-Silico Drug Repurposing Approach

preprint
submitted on 06.04.2020 and posted on 09.04.2020 by Cesar Mendoza-Martinez, Alejandro Rodriguez-Lezama
An in-silico drug repurposing study was carried out to search for potential COVID-19 antiviral agents. A dataset of 1615 FDA-approved drugs was docked in the active site of SARS CoV-2 Main protease. A subset of the top scoring hit compounds was subjected to follow-up molecular dynamics simulations to further characterise the predicted binding modes. The main findings are that the drugs Aliskiren, Capreomycin, Isovuconazonium, emerge as novel potential inhibitors. We also observed that Ceftolozane, Cobicistat, Carfilzomib and Saquinavir are well-ranked by our protocol, in agreement with other recent in silico drug repurposing studies, however MD simulations shows only potential for the three first, as Saquinavir exhibited an unstable binding mode. As many HIV-protease inhibitors has been reported as active and not active, Atazanavir and Lopinavir were included in the data set in order to rationalize the findings. In addition, our protocol ranked favourably Dronedarone suggesting that this recently reported SARS-CoV-2 inhibitor targets SARS-CoV-2 Main protease.

History

Email Address of Submitting Author

Cesar.Mendoza@ed.ac.uk

Institution

TECSIQUIM S.A. de C.V. and The University of Edinburgh

Country

Mexico

ORCID For Submitting Author

0000-0003-3439-9809

Declaration of Conflict of Interest

There is no conflict of interests

Version Notes

Revision01. First revision only

Exports