Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study.
| Autor: | Askari FS; Vista Aria Rena Gene Inc., Gorgan, 4918653885, Golestan Province, Iran., Ebrahimi M; Neonatal & Children's Health Research Center, Golestan University of Medical Sciences, Gorgan, 4918936316, Iran., Parhiz J; Neonatal & Children's Health Research Center, Golestan University of Medical Sciences, Gorgan, 4918936316, Iran., Hassanpour M; Vista Aria Rena Gene Inc., Gorgan, 4918653885, Golestan Province, Iran., Mohebbi A; Vista Aria Rena Gene Inc., Gorgan, 4918653885, Golestan Province, Iran., Mirshafiey A; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1417613151, Iran. |
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| Jazyk: | angličtina |
| Zdroj: | Future virology [Future Virol] 2022 Jul. Date of Electronic Publication: 2022 Aug 08. |
| DOI: | 10.2217/fvl-2022-0054 |
| Abstrakt: | 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. (© 2022 Future Medicine Ltd.) |
| Databáze: | MEDLINE |
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