Identification of potential 3CLpro inhibitors-modulators for human norovirus infections: An advanced virtual screening approach

Abstract

The present study aimed to screen small molecular compounds as the human noroviruses (HuNoV) inhibitors/modulators that could be potentially responsible for exhibiting some level of inhibitory activity against HuNoV 3CLPro. The structural similarity-based screening against ChEMBL database is performed against known chemical entities which are presently under pre-clinical trial. Molecules that remained after the similarity search were considered molecular docking using SCORCH and PLANTS. On detailed analyses and comparisons with control molecule, 3 hits (CHEMBL393820, CHEMBL2028556 and CHEMBL3747799) were found to be potential for HuNoV 3CLpro inhibition. The binding interaction analysis revealed several critical amino acids to hold the molecules tightly at the close proximity site of the catalytic residues. Further, three MD simulation study was performed in triplicate to understand the binding stability and potentiality of the proposed molecule towards HuNov 3CLpro. The binding free energy based on MM-GBSA has revealed their strong interaction affinity with 3CLpro.