"Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CLpro and PLpro."

Journal of Molecular Structure
Deep BhowmikDiwakar Kumar

Abstract

The sudden increase in the COVID-19 epidemic affected by novel coronavirus 2019 has jeopardized public health worldwide. Hence the necessities of a drug or therapeutic agent that heal SARS-CoV-2 infections are essential requirements. The viral genome encodes a large Polyprotein, further processed by the main protease/ 3C-like protease (3CLpro) and papain-like proteases (PLpro) into 16 nonstructural proteins to form a viral replication complex. These essential functions of 3CLpro and PLpro in virus duplication make these proteases a promising target for discovering potential therapeutic candidates and possible treatment for SARS-CoV-2 infection. This study aimed to screen a unique set of protease inhibitors library against 3CLpro and PLpro of the SARS-CoV-2. A molecular docking study was performed using PyRx to reveal the binding affinity of the selected ligands and molecular dynamic simulations were executed to assess the three-dimensional stability of protein-ligand complexes. The pharmacodynamics parameters of the inhibitors were predicted using admetSAR. The top two ligands (Nafamostat and VR23) based on docking scores were selected for further studies. Selected ligands showed excellent pharmacokinetic properties with proper...Continue Reading

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Software Mentioned

PROCHECK
Pymol Molecular Visualization
CUDA
YASARA
AutoDockVina
Ligplot
OS Centos
Molinspiration
Nafamostat
admetSAR

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