Computational investigation of nsP2 inhibitors for Chikungunya virus treatment: advancing therapeutic strategies against viral infections

Abstract

Chikungunya virus (CHIKV) is an insect-borne virus characterized by a positive-sense single-stranded RNA genome, primarily transmitted to humans through the bites of Aedes aegypti and Aedes albopictus mosquitoes. Initially reported in Tanzania in 1952, the virus has since disseminated across various tropical and subtropical regions worldwide, leading to clinical manifestations such as high-grade fever, arthralgia, and myalgia. The virus encodes four non-structural proteins (nsP1–nsP4), which are integral to its replication cycle, immune evasion mechanisms, and RNA synthesis. Among these, nsP2 is particularly significant due to its dual functionality as a protease and helicase, making it a viable target for antiviral drug development in the absence of currently approved therapeutic agents. To explore potential inhibitors, a molecular docking study was undertaken utilizing the crystal structure of the nsP2 protease (PDB ID: 3TRK), resolved at a 2.4 Å resolution. A curated library of 202 FDA-approved compounds was subjected to virtual screening, resulting in the identification of five lead compounds with the highest binding affinities. These candidates exhibited robust interactions with critical residues in the nsP2 active site, highlighting their potential as promising antiviral agents against CHIKV.