Chikungunya Virus (CHIKV) was firstly reported in 1952 in Tanzania, East Africa as the causative agent of Chikungunya fever (CHIKV). CHIKV belongs to the genus Alphavirus of the family Togaviridae and is an enveloped virus with a single-stranded positive-sense RNA genome. Currently no suitable drugs or vaccines against Chikungunya virus which makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has classified as a crucial drug target to combat infections caused by α-viruses including Chikungunya virus due to its involvement viral replication. Here in, we explore the structure of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the plant based ligands (Dillenia pentagyna) were designed and screened by use of Chem-sketch software (ACD labs, ARGUS lab) and subjected to docking with the homology modeled Chikungunya nsP2 protease using Pyrx-viana4.0. The interaction profiling of ligands(Dillenia pentagyna phytocompounds) with the protein was carried out using Discovery studio4.5 . The results demonstrated that the Phytocompounds (Dillinia-5,7,8) possessed mean highest binding affinity (-7.2,-7.8,-8.3) towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that Dillenia pentagyna phytocompounds inhibit the nsP2 protease by binding to its active pocket site. Moreover, further investigation required for binding energy optimization that may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.
Keywords: Chikungunya, nsP2 protease, Homology modeling, Pyrx-viana4.0, Molecular dynamics simulation