RNA-DEPENDENT RNA POLYMERASE (RDRP) INHIBITOR DRUGS AGAINST SARS-COV-2: A MOLECULAR DOCKING STUDY

Abstract

Objective: SARS-CoV-2 associated viral pandemic was first reported in Wuhan, China, in December 2019. Due to the rapid increase in its pathogenicity, SARS-CoV-2 was declared a global pandemic by WHO on March 11, 2020. For that reason, determining the most attractive viral protein targets became a must. One of the most important target proteins is SARS-COV-2 RNA-dependent RNA polymerase (RdRp) on which COVID-19 depends in its replication process. This study aimed to examine the possible interactions between RdRp and the most promising RdRp nucleoside inhibitors especially Purine nucleoside analogs, to detect the most important residues that commonly interact with RdRp's inhibitors and to investigate whether if there any mutations have been observed so far in these residues or not. Material and Method: Molecular docking studies were carried out using AutoDock Vina between SARS-CoV-2 RdRp and drugs approved against different viral RdRps (Galidesivir, Remdesivir, Ribavirin, Sofosbuvir, and Favipiravir) as well as physiological nucleotides (ATP and GTP). Based on the obtained results, a detailed surface-interaction analysis was also performed using Pymol and Discovery Studio Visualizer software for the models that exhibited the most suitable location and configuration in space. Result and Discussion: All the tested molecules were able to bind to SARS-CoV-2 RdRp successfully. Also, they all commonly interact with 9 different amino acids (Arg553, Arg555, Asp618, Asp623, Ser682, Asn691, Ser759, Asp760, and Asp761), and 3 different Template-primer RNA nucleotides (U10, A11, and U20) causing inhibition of viral RdRp via non obligate RNA chain termination.