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

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(pro)) and papain-like protease (PL(pro)) 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(pro) 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(pro)-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(pro). 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(pro) were identified. This study suggests a safe antimalarial drug, namely epoxomicin, as a probable inhibitor of SARS-CoV-2 M(pro) 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.