Molecular dynamics simulations and MM-GBSA reveal novel guanosine derivatives against SARS-CoV-2 RNA dependent RNA polymerase

Abdo A Elfiky; Hanan A Mahran; Ibrahim M Ibrahim; Mohamed N Ibrahim; Wael M Elshemey

doi:10.1039/d1ra07447d

Molecular dynamics simulations and MM-GBSA reveal novel guanosine derivatives against SARS-CoV-2 RNA dependent RNA polymerase

RSC Adv. 2022 Jan 20;12(5):2741-2750. doi: 10.1039/d1ra07447d. eCollection 2022 Jan 18.

Authors

Abdo A Elfiky¹, Hanan A Mahran¹, Ibrahim M Ibrahim¹, Mohamed N Ibrahim^{2

3}, Wael M Elshemey^{1

4}

Affiliations

¹ Biophysics Department, Faculty of Science, Cairo University Giza Egypt abdo@sci.cu.edu.eg dr_abdo@cu.edu.eg +20 1003260523.
² Clinical Laboratories Department, College of Applied Medical Sciences, Jouf University Sakakah Kingdom of Saudi Arabia.
³ Microbiology Department, Faculty of Science, Ain Shams University Cairo Egypt.
⁴ Physics Department, Faculty of Science, Islamic University in Madinah KSA.

Abstract

According to the World Health Organization (WHO), SARS-CoV-2 is responsible for more than 5 M deaths and is reported in 223 countries infecting 250+ M people. Despite the current vaccination momentum, thousands of people die every day by COVID-19. Suggesting possible blockers of the viral RNA-dependent RNA polymerase is highly needed for potential effective therapeutics against SARS-CoV-2. This study utilizes combined molecular dynamics simulation and molecular docking to test novel guanosine derivatives against SARS-CoV-2 RdRp. Results reveal the binding potency of nineteen guanosine derivatives against SARS-CoV-2 solved structures. The bulky moieties (hydroxyl or fluorated phenyl moieties) added to the 2' position of the ribose ring positively impacted the binding affinity to RdRp. The current in silico study represents a one-step-ahead for suggesting new possible blockers of SARS-CoV-2 RdRp that are yet to be verified in the wet lab. It offers new potential binders or blockers of RdRp that bind to the protein active site tighter than remdesivir. The latter was approved by the food and drug administration (FDA) for emergency use against COVID-19 last year.