Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study.
Fatemeh Sana AskariMohsen EbrahimiJabbar ParhizMina HassanpourAlireza MohebbiAbbas MirshafieyPublished in: Future virology (2022)
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.
Keyphrases
- sars cov
- molecular dynamics
- respiratory syndrome coronavirus
- global health
- drug discovery
- oxide nanoparticles
- small molecule
- end stage renal disease
- newly diagnosed
- life cycle
- density functional theory
- ejection fraction
- public health
- dengue virus
- coronavirus disease
- risk assessment
- peritoneal dialysis
- molecular docking
- high throughput
- zika virus
- crystal structure
- aedes aegypti