Integrated computational approach towards repurposing of antimalarial drug against SARS-CoV-2 main protease.

Unlabelled: Huge vaccination drives are underway around the world for the ongoing COVID-19 pandemic. However, the search for antiviral drugs is equally crucial. As new drug discovery is a time-consuming process, repurposing of existing drugs or developing drug candidates against SARS-CoV-2 will make the process faster. Considering this, 63 approved and developing antimalarial compounds were selected to screen against main protease (M) and papain-like protease (PL) of SARS-CoV-2 using in silico methods to find out possible new drug candidate(s). Out of 63 compounds, epoxomicin showed the best binding affinity against the M with CDocker energy of - 57.511 kcal/mol without any toxic effect. This compound was further taken for molecular dynamic simulation study, where the M-epoxomicin complex was found to be stable with binding free energy - 79.315 kcal/mol. The possible inhibitory potential of the selected compound was determined by 3D-QSAR analysis and found to be 0.4447 µM against SARS-CoV-2 M. Finally, the structure activity relationship of the compound was analyzed and two fragments responsible for overall good binding affinity of the compound at the active site of M were identified. This study suggests a safe antimalarial drug, namely epoxomicin, as a probable inhibitor of SARS-CoV-2 M which needs further validation by in vitro/in vivo studies before clinical use.

Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-01916-0.