MOLECULAR DOCKING AND SCREENING OF DRUGS FOR 6LU7 PROTEASE INHIBITOR AS A POTENTIAL TARGET FOR COVID-19 Original Article MANOJ GADEWAR 1 , BHARAT LAL 2 1 Department of Pharmacology, K. R. Mangalam University, Gurugram, Haryana, India, 2 Department of Pharmaceutics, K. R. Mangalam University, Gurugram, Haryana, India Email: manojgadewar@gmail.com Received: 14 Sep 2021, Revised and Accepted: 25 Oct 2021 ABSTRACT Objective: The aim of present investigation is docking of various existing antiviral, anti-tubercular and anti-malarial drugs on 6LU7 receptor of SARS-CoV-2 in the treatment of COVID-19. Methods: In this study, the structure of coronavirus binding protein and ligands for various drugs were collected from the protein data bank and pub chem. Molecular docking was carried out using Schrodinger 9.0 software. In molecular docking study, 19 different drugs of various categories like antiviral, anti-malarial and anti-tubercular were investigated for analyzing binding to 6LU7 receptors of COVID-19. Results: The docking result showed a high affinity of zanamivir, montelukast, ramdesvir, ritonavir, cobicistat and favipravir to the 6LU7 receptor of novel coronavirus. Thus the combination of these drugs may be useful in preventing further infection and can be used as a potential target for further in vitro and in vivo studies of SARS-CoV-2. Conclusion: Treatment of COVID-19 has been challenge due to the non-availability of effective drug therapy. In this study, we reported drugs for targeting 6LU7 Mpro/3Clpro protein, which showed prominent effects as potential inhibitors of COVID-19 Mpro. Keywords: COVID-19, RNA dependant RNA polymerase, Molecular docking, Antiviral, Anti-malarial © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2022v14i1.43132. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Since December 2019, an epidemic of corona has been spreading all across the globe. China reported a case of pneumonia of unknown cause on 31st Dec 2019 in some patient operating in Huanan seafood market of Wuhan in Hubei province and caused outbreak of a novel corona (nCOVID-19). After genome analysis it was found that causative agent for the infection was zoonotic coronavirus and this novel Coronavirus (2019-nCoV) which resembles similarity with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV) but with fast transmission and rapid rate of infection. On 11 th March 2020 WHO characterized COVID-19 outbreak is a pandemic and released interim guidelines on critical preparedness, readiness and response actions to keep people safe from the COVID-19 [1, 2]. Due to the characteristic appearance of crown-like spikes around the virion it is renamed as corona virus. Coronaviruses belongs to the sub family Orthocoronavirinae, of the family Coronaviridae, order Nidovirales. Coronaviruses are spherical-shaped viruses having size around 120 nm diameters. These are lipid bilayered viruses consist of membrane (M), envelope (E) and spike (S) structural proteins. Inside the envelope it contains nucleocapsid formed from multiple copies of the nucleocapsid (N) protein, which are anchored with a positive-sense single- stranded RNA genome in a continuous beads-on-a-string type conformation. The genome size of coronaviruses is largest among RNA viruses which ranges approximately from 27 to 34 kilobases3and it has a 5′ methylated cap and a 3′ polyadenylated tail fig. 1 [3]. Fig. 1: Structure of COVID-19 Genetically they are classified into four major genera Alpha, Beta, Gamma, and Delta coronavirus; the former two genera primarily infect mammals, whereas the latter two predominantly infect birds. Six kinds of human coronavirus have been previously identified, which include HCoV-NL63 and HCoV229E (Alpha coronavirus) and HCoV-OC43, HCoVHKU1, SARS-CoV, MERS-CoV (Beta coronavirus) and COVID-19 is seventh [4]. The life cycle of COVID-19 begins in host cells once it reaches to lungs and binds to the type-II pneumocytes of the alveoli using its International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 14, Issue 1, 2022