1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Molecular docking studies of novel drug derivative bound to main protease enzyme (Mpro) in Covid-19
Paper ID : 1077-ICB10
Authors:
Reza Sahebi *
Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract:
Background: COVID-19 antiviral drugs have recently been discovered and introduced in light of their reported high virulence in recent months. The 3C-like protease (Mpro/7L8I) is a promising target for anti-CoV drugs. The goal of this study is to inhibit COVID-19 with FDA-approved viral antiprotease drugs and their derivative.
Materials and Methods: This is a descriptive-analytic research project. PubChem and the Protein Data Bank (PDB) were used to obtain the tertiary structure of COVID-19 Mpro as well as the drug's compounds. Molecular docking was screened using MVD (molegro virtual docker), version 6, with a grid resolution of 0.30 Å. The calculated ligand receptor (protein) interaction energy is represented by docking scores (DOS). As a result, more negative scores indicate a stronger binding tendency.
Results: The docking of COVID-19 protease (7L8I) investigated with three selected FDA-approved viral antiprotease drugs (Lopinavir, Cobicistat, and Ritonavir) followed by a cobicistat derivative. Cobicistat and cobicistat derivative had the best DOS (-188.89 and -215.12 respectively) and Lopinavir and Ritonavir had the worst DOS (7252 and 3199 respectively). Mpro could be targeted with 11 different conformations at its binding site by the best-screened ligand, a cobicistat derivative (InChIKey=ZHYPAEQWZKWGPZUHFFFAOYNA-N), which was identified as the most effective.
Conclusion: The findings revealed that one of the three FDA-approved drugs selected for the study can be a potent inhibitor of COVID-19. Among them, a cobicistat derivative may be the most effective for the treatment of the disease. On the basis of the findings, it is recommended that in-vitro and in-vivo studies be carried out to determine the efficacy of this drug against the COVID-19 infection virus.
Keywords:
Cobicistat; Ritonavir; Lopinavir; Molecular Docking; Main Protease; Anti Viral Drugs
Status : Paper Accepted (Poster Presentation)