Key result
Virtual screening identifies three compounds as potential human norovirus 3CLpro inhibitors.
Why the study?
The study aimed to screen small molecular compounds as human norovirus inhibitors or modulators with potential inhibitory activity against HuNoV 3CLpro.
Advanced virtual screening and molecular dynamics simulations identified three ChEMBL compounds as potential inhibitors of human norovirus 3CLpro.
Hypothesis-generating for norovirus antivirals; requires experimental validation before any therapeutic consideration.
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.
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Bhowmick et al. (2023) studied Human norovirus infection. CHEMBL393820, CHEMBL2028556, and CHEMBL3747799 vs. PPNDs was evaluated on Binding affinity and stability with HuNoV 3CLpro. Virtual screening and molecular dynamics simulations identified three compounds (CHEMBL393820, CHEMBL2028556, and CHEMBL3747799) as potential inhibitors of human norovirus 3CLpro.
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