Biological and Medicinal Chemistry

Identification of FDA Approved Drugs Targeting COVID-19 Virus by Structure-Based Drug Repositioning



The new strain of Coronaviruses (SARS-CoV-2), and the resulting Covid-19 disease has spread swiftly across the globe after its initial detection in late December 2019 in Wuhan, China, resulting in a pandemic status declaration by WHO within 3 months. Given the heavy toll of this pandemic, researchers are actively testing various strategies including new and repurposed drugs as well as vaccines. In the current brief report, we adopted a repositioning approach using insilico molecular modeling screening using FDA approved drugs with established safety profiles for potential inhibitory effects on Covid-19 virus. We started with structure based drug design by screening more than 2000 FDA approved drugs against Covid-19 virus main protease enzyme (Mpro) substrate-binding pocket focusing on two potential sites (central and terminal sites) to identify potential hits based on their binding energies, binding modes, interacting amino acids, and therapeutic indications. In addition, we elucidate preliminary pharmacophore features for candidates bound to Covid-19 virus Mpro substrate-binding pocket. The top hits bound to the central site of Mpro substrate-binding pocket include antiviral drugs such as Darunavir, Nelfinavir and Saquinavir, some of which are already being tested in Covid-19 patients. Interestingly, one of the most promising hits in our screen is the hypercholesterolemia drug Rosuvastatin. In addition, the top hits bound to the terminal site of Mpro substrate-binding pocket include the anti-asthma drug Montelukast and the anti-histaminic Fexofenadine among others. These results certainly do not confirm or indicate antiviral activity, but can rather be used as a starting point for further in vitro and in vivo testing, either individually or in combination.

Version notes

Version 2 expanded docking analysis to include the terminal domain of the Mpro substrate binding pocket which revealed additional potential hits


Thumbnail image of COVID-19 Docking-April 26 - Version 3 .pdf