Identification of Pyrazole Derivative as an Antiviral Agent Against Chikungunya Through HTVS

Title:Identification of Pyrazole Derivative as an Antiviral Agent Against Chikungunya Through HTVS

Volume: 12 Issue: 4

Author(s): Surender Singh Jadav, Barij Nayan Sinha, Boris Pastorino, Xavier de Lamballerie, Rolf Hilgenfeld and Venkatesan Jayaprakash

Affiliation:

Keywords: Antiviral, chikungunya, HTVS, molecular docking, pyrazole derivatives, synthesis.

Abstract: 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.

Cite this article as:

Singh Jadav Surender, Nayan Sinha Barij, Pastorino Boris, de Lamballerie Xavier, Hilgenfeld Rolf and Jayaprakash Venkatesan, Identification of Pyrazole Derivative as an Antiviral Agent Against Chikungunya Through HTVS, Letters in Drug Design & Discovery 2015; 12 (4) . https://dx.doi.org/10.2174/1570180811666141001005402

DOI https://dx.doi.org/10.2174/1570180811666141001005402	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X