title: Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors.
abstract: Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot(+). The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela-769 008, India.
authors.forename: T
authors.initials: T
authors.lastname: Agarwal
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela-769 008, India.
authors.forename: Somya
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela-769 008, India.
authors.forename: A
authors.initials: A
authors.lastname: Bissoyi
keywords: AutoDock4.2; Chikungunya; Homology modeling; Molecular dynamics simulation; nsP2 protease