Molecular docking study of some antiviral drugs against SARS-CoV-۲ RNA-dependent RNA polymerase protein

Backgrounds: In late ۲۰۱۹, the world faced a pandemic called the new coronavirus (SARS-coV-۲). Unfortunately, no effective drug has been approved for this disease so far, and the treatmentoptions are very limited. One of the most important coronavirus proteins is RNA dependentRNA polymerase (RdRp). RdRp is responsible for replicating the genomic (+) ssRNA. Analternative way to quickly identify potentially approved drugs is to use a drug repositioning thatmanages new and emerging diseases.Materials and Methods: In this study, RdRp was selected as the target and virtual screeningwas performed. The ۳D structure of the RdRp was obtained from the protein data bank (PDB ID:۶M۷۱ resolution ۲.۹۰ A) and its energy was minimized. ۱۰ antiviral drugs as inhibitors wereselected and their ۳D structure was extracted from Drag Bank and their energy was minimized.Autodock ۴.۲ software was used to evaluate the affinity of antiviral drugs for RdRp. The bindingsite of the ligands to the RdRp was determined in the gridbox and its dimensions were set in GPFformat. Finally, the algorithm was implemented and the results were analyzed.Results: Among the ۱۰ drugs Lopinavir, Saquinavir, Nelfinavir, Remdesivir, Amprenavir,Indinavir, Dasabuvir, Dolutegravir, Drarunavir, Ritonavir the first three drugs are superior andmore effective. Hydrogen bonds, binding energy and inhibition constant (Ki) of these threedrugs, including ۰, -۹.۷۵ kcal/mol, ۷۱.۵۲ nM (Lopinavir), ۳, -۹.۷۳ kcal/mol, ۷۳.۴۳ nM(Saquinavir), ۵, -۹.۰۶ kcal/mol, ۲۲۷.۶۲nM (Nelfinavir) respectively.Conclusion: Our studies show Lopinavir, Saquinavir, Nelfinavir work very well on RdRp andare recommended that more detailed studies, including animal and human studies, be performed.

کلیدواژه ها:

SARS-CoV-۲ ، Molecular docking ، RdRp ، Saquinavir