SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective

Abstract

New treatment against SARS-CoV-2 now is a must. Nowadays, the world encounters a huge health crisis by the COVID-19 viral infection. Nucleotide inhibitors gave a lot of promising results in terms of its efficacy against different viral infections. In this work, molecular modeling, docking, and dynamics simulations are used to build a model for the viral protein RNA-dependent RNA polymerase (RdRp) and test its binding affinity to some clinically approved drugs and drug candidates. Molecular dynamics is used to equilibrate the system upon binding calculations to ensure the successful reproduction of previous results, to include the dynamics of the RdRp, and to understand how it affects the binding. The results show the effectiveness of Sofosbuvir, Ribavirin, Galidesivir, Remdesivir, Favipiravir, Cefuroxime, Tenofovir, and Hydroxychloroquine, in binding to SARS-CoV-2 RdRp. Additionally, Setrobuvir, YAK, and IDX-184, show better results, while four novel IDX-184 derivatives show promising results in attaching to the SARS-CoV-2 RdRp. There is an urgent need to specify drugs that can selectively bind and subsequently inhibit SARS-CoV-2 proteins. The availability of a punch of FDA-approved anti-viral drugs can help us in this mission, aiming to reduce the danger of COVID-19. The compounds 2 and 3 may tightly bind to the SARS-CoV-2 RdRp and so may be successful in the treatment of COVID-19.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19
• SARS-CoV-2
• RdRp
• molecular docking
• molecular dynamics simulation
• drug repurposing

Acknowledgements

MDS calculations are conducted on the supercomputing facility of the Bibliotheca Alexandrina, Alexandria, Egypt. This work is done during the Junior associate award granted to the author for the period 2016–2021 from the Abdus Salam International Center for Theoretical Physics (ICTP), Trieste, Italy.

Competing interest

The author declares that there is no competing interest in this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.