Digging for the Discovery of SARS-CoV-2 nsp12 Inhibitors: A Pharmacophore-Based and Molecular Dynamics Simulation Study
Fatemeh Sana Askari, Mohsen Ebrahimi, Jabbar Parhiz, Mina Hassanpour, Alireza Mohebbi, Abbas Mirshafiey
Abstract
Aim: COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. Objective: to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. Methods: 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. Results: ZINC03977803 was nominated as the lead compound. The results showed stable interaction between ZINC03977803 and nsp12 during 10 ns. Discussion: 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.