br A novel coronavirus, SARS-CoV-2 has caused a recent pandemic called COVID-19 and a severe health threat around the world In the current situation, the virus is rapidly spreading worldwide, and the discovery of vaccine and potential therapeutics are critically essential The crystal structure for main protease (M supro /su) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CL supro /su) was recently made available and is considerably similar to previously reported SARS-CoV Due to its essentiality in viral replication, it represents a potential drug target Herein, computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs Molecular docking of 13 antivirals against 3-chymotrypsin-like cysteine protease (3CL supro /su) enzyme was accomplished and indinavir was described as a lead drug with a docking score of -8 824 and a XGscore of -9 466 kcal/mol Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus a new library of HEA compounds ( 2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir Exclusively, compound 16 with docking score of -8 955 adhered to drug like parameters, and the Structure-Activity Relationshi(SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein Molecular Dynamics (MD) simulation studies carried out at 100ns supported the stability of 16 within the binding pocket Largly, our results supported that this novel compound 16 binds to the domain & II, and domain II-IIlinker of 3CL supro /suprotein, suggesting its suitablity as strong candidate for therapeutic discovery against COVID-19 Lead compound 16 could pave incredible directions for the design of novel 3CL supro /suinhibitors and ultimately therapeutics against COVID-19 disease br /
Discovery of New Hydroxyethylamine Analogs Against 3CLpro Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation and Structure-Activity RelationshiStudies