Abstract
Coronavirus disease strain (SARS-CoV-2) was discovered in 2019, and it is spreading very fast around the world causing the disease Covid-19. Currently, more than 1.6 million individuals are infected, and several thousand are dead across the globe because of Covid-19. Here, we utilized the in-silico approaches to identify possible protease inhibitors against SARS-CoV-2. Potential compounds were screened from the CHEMBL database, ZINC database, FDA approved drugs and molecules under clinical trials. Our study is based on 6Y2F and 6W63 co-crystallized structures available in the protein data bank (PDB). Seven hundred compounds from ZINC/CHEMBL databases and fourteen hundred compounds from drug-bank were selected based on positive interactions with the reported binding site. All the selected compounds were subjected to standard-precision (SP) and extra-precision (XP) mode of docking. Generated docked poses were carefully visualized for known interactions within the binding site. Molecular mechanics-generalized born surface area (MM-GBSA) calculations were performed to screen the best compounds based on docking scores and binding energy values. Molecular dynamics (MD) simulations were carried out on four selected compounds from the CHEMBL database to validate the stability and interactions. MD simulations were also performed on the PDB structure 6YF2F to understand the differences between screened molecules and co-crystallized ligand. We screened 300 potential compounds from various databases, and 66 potential compounds from FDA approved drugs. Cobicistat, ritonavir, lopinavir, and darunavir are in the top screened molecules from FDA approved drugs. The screened drugs and molecules may be helpful in fighting with SARS-CoV-2 after further studies.Communicated by Ramaswamy H. Sarma.
Keywords: Covid-19; Drug Repurposing; MD Simulations; Virtual Screening.
【저자키워드】 COVID-19, Drug repurposing, MD simulations, virtual screening., 【초록키워드】 coronavirus disease, Structure, SARS-CoV-2, Zinc, Lopinavir, Ritonavir, clinical trials, Virtual screening, drug, docking, molecular dynamics, database, protease inhibitors, MD simulations, ZINC database, FDA approved drug, Screening, Cobicistat, MD simulation, binding site, binding energy, approved drugs, Protease inhibitor, Protein, stability, molecules, in-silico, disease, interactions, Molecular mechanics, Ligand, FDA approved Drugs, Interaction, darunavir, Protein Data Bank, surface area, individual, Compound, docking scores, docking score, positive, dead, PDB, PDB structure, selected, identify, performed, approach, carried, globe, reported, the disease, screened, Potential, co-crystallized, docked, 【제목키워드】 inhibitor,