In silico Drug Repurposing for COVID-19: Targeting SARS- CoV-2 Proteins through Docking and Quantum Mechanical Scoring. ChemRxiv.

CAVASOTTO, CLAUDIO N.; DI FILIPPO, JUAN I.

ChemRxiv

ChemRxiv

Año: 2020

2573-2293

In December 2019, an infectious disease caused by the coronavirus SARS-CoV-2 appearedin Wuhan, China. This disease (COVID-19) spread rapidly worldwide, and on March 2020 wasdeclared a pandemic by the World Health Organization (WHO). Today, more than 4.7 millionpeople have been infected, with almost 320,000 casualties, while no vaccine nor antiviral drugis in sight. The development of a vaccine might take at least a year, and even longer for a noveldrug; thus, finding a new use to an old drug (drug repurposing) could be the most effectivestrategy. We present a high-throughput docking approach using a novel quantum mechanicalscoring for screening a chemical library of 11,500 molecules built from FDA-approved drugsand compounds undergoing clinical trials, against three SARS-CoV-2 target proteins: thespike or S-protein, and two proteases, the main protease and the papain-like protease. TheS-protein binds directly to the Angiotensin Converting Enzyme 2 receptor of the human hostcell surface, while the two proteases process viral polyproteins. Following the analysis of ourstructure-based virtual screening, we propose several structurally diverse compounds that coulddisplay antiviral activity against SARS-CoV-2. Clearly, these compounds should be furtherevaluated in experimental assays and clinical trials to confirm their actual activity againstthe disease. We hope that these findings may contribute to the rational drug design againstCOVID-19