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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Vol. 17, No. 10

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Received 13 March 2022

Accepted 22 July 2022

Published online 8 August 2022

Published in print October 2022

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fvl-2022-0054

Author contributions

FS Askari: formal analysis, investigation, resources, writing - original draft. M Ebrahimi: investigation, data curation. J Parhiz: investigation, writing - original draft. M Hassanpour: investigation, writing - original draft. A Mirshafiey and A Mohebbi: methodology, resources, software, writing – review and editing, visualization. A Mirshafiey and A Mohebbi: conceptualization, validation, project administration, supervision.

Data sharing & availability

Data and materials will provided upon reasonable request.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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