Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study.

COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. A virtual screening of ZINC natural products on SARS-CoV-2 nsp12's druggable cavity was performed. A lead compound with the highest affinity to nsp12 was simulated dynamically for 10 ns. ZINC03977803 was nominated as the lead compound. The results showed stable interaction between ZINC03977803 and nsp12 during 10 ns. ZINC03977803 showed stable interaction with the catalytic subunit of SARS-CoV-2, nsp12. It could inhibit the SARS-CoV-2 life cycle by direct interaction with nsp12 and inhibit RdRp complex formation.