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

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 scr...

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Autores principales: Askari, Fatemeh Sana, Ebrahimi, Mohsen, Parhiz, Jabbar, Hassanpour, Mina, Mohebbi, Alireza, Mirshafiey, Abbas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Future Medicine Ltd 2022
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370102/
https://www.ncbi.nlm.nih.gov/pubmed/35983350
http://dx.doi.org/10.2217/fvl-2022-0054
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author Askari, Fatemeh Sana
Ebrahimi, Mohsen
Parhiz, Jabbar
Hassanpour, Mina
Mohebbi, Alireza
Mirshafiey, Abbas
author_facet Askari, Fatemeh Sana
Ebrahimi, Mohsen
Parhiz, Jabbar
Hassanpour, Mina
Mohebbi, Alireza
Mirshafiey, Abbas
author_sort Askari, Fatemeh Sana
collection PubMed
description 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.
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spelling pubmed-93701022022-08-16 Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study Askari, Fatemeh Sana Ebrahimi, Mohsen Parhiz, Jabbar Hassanpour, Mina Mohebbi, Alireza Mirshafiey, Abbas Future Virol Research Article 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. Future Medicine Ltd 2022-08-08 2022-07 /pmc/articles/PMC9370102/ /pubmed/35983350 http://dx.doi.org/10.2217/fvl-2022-0054 Text en © 2022 Future Medicine Ltd https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Research Article
Askari, Fatemeh Sana
Ebrahimi, Mohsen
Parhiz, Jabbar
Hassanpour, Mina
Mohebbi, Alireza
Mirshafiey, Abbas
Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
title Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
title_full Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
title_fullStr Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
title_full_unstemmed Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
title_short Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
title_sort digging for the discovery of sars-cov-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370102/
https://www.ncbi.nlm.nih.gov/pubmed/35983350
http://dx.doi.org/10.2217/fvl-2022-0054
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