Identification of Pyrazole Derivative as an Antiviral Agent Against Chikungunya Through HTVS
Surender Singh Jadav,
Barij Nayan Sinha,
Xavier de Lamballerie,
Structure based High-throughput Virtual Screening (HTVS) of ChikV nsP2 protease (PDB: 3TRK) with two
publicly available database ZINC12 and BindingDB has been carried out to identify suitable inhibitors for the treatment of
chikungunya infection. HTVS protocol implemented in GLIDE 5.0 (Schrodinger LLC) has been employed to screen the
drug-like subset of ZINC12 (10,090,210) and protease inhibitors in BindingDB (83,000). One of the chemical scaffolds
from the list of different chemical classes was selected for the synthesis of (ZINC04725220, compound 11). Few more
schiff’s bases (13-21) were also synthesized with the intermediate 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (4-6) and
tested for anti-ChikV (strain OPY1, Reunion Island 2006) activity using Cytopathic effect reduction (CPE) assay. Surprisingly,
only compound 11(IC50: 5µg/ml ie 14.15 µM) has shown inhibitory activity against ChikV. Further precise docking
of compound 11 with target protein was carried out to understand the molecular interactions important for activity.
Keywords: Antiviral, chikungunya, HTVS, molecular docking, pyrazole derivatives, synthesis.
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