Jadav S. S., Sinha B. N., Pastorino B., de Lamballerie Xavier, Hilgen-Feld R., Jayaprakash V. (2015). Identification of pyrazole derivative as an antiviral agent against chikungunya through HTVS. Letters in Drug Design and Discovery, 12 (4), p. 292-301. ISSN 1570-1808.
Titre du document
Identification of pyrazole derivative as an antiviral agent against chikungunya through HTVS
Jadav S. S., Sinha B. N., Pastorino B., de Lamballerie Xavier, Hilgen-Feld R., Jayaprakash V.
Source
Letters in Drug Design and Discovery, 2015,
12 (4), p. 292-301 ISSN 1570-1808
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: 5 mu g/ml ie 14.15 mu M) 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.
