Identification of Potential FDA-Approved Inhibitors of SARS-CoV-2 Helicase Through a Multistep In silico Approach: A Promising Prospect for COVID-19 Treatment.

Abstract

Introduction: In this research aiming at combating COVID-19, we employed advanced computer-based methods to identify potential inhibitors of SARS-CoV-2 helicase from a pool of 3009 clinical and FDA-approved drugs.

Methods: To narrow down the candidates, we focused on VXG, the helicase's co-crystallized ligand, and sought compounds with chemical structures akin to VXG within the examined drugs. The initial phase of our study involved molecular fingerprinting in addition to structure similarity studies.

Results: Once the compounds most closely resembling VXG (29 compounds) were identified, we conducted various studies to investigate and validate the binding potential of these selected compounds to the protein's active site. The subsequent phase included molecular docking, molecular dynamic (MD) simulations, and MM-PBSA studies against the SARS-CoV-2 helicase (PDB ID: 5RMM).

Conclusion: Based on our analyses, we identified nine compounds with promising potential as SARS-CoV-2 helicase inhibitors, namely aniracetam, aspirin, chromocarb, cinnamic acid, lawsone, loxoprofen, phenylglyoxylic acid, and antineoplaston A10. The findings of this research help the scientific community to further investigate these compounds, both in vitro and in vivo.