Exploration of potential inhibitors against chikungunya envelope: an in-silico clue

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne virus which causes chikungunya disease. Two biological vectors Aedes aegypti and Aedes albopictus transmit CHIKV to the victim body. According to the report of the European Centre for Disease Prevention and Control, epidemics of chikungunya disease existed in 2024 over America, Africa, Europe and Asia. Although 50% CHIKV infected person show chronic clinical symptoms and several troubles associated with chikungunya, still there are no effective vaccines or medications on market. So availability of another CHIKV inhibiting materials and mechanisms are necessary. For this purpose recently plant-derived bioactive compounds with antiviral properties are used to inhibit chikungunya infection. In this present research work 69 CHIKV inhibiting active compounds were chosen for ADMET analysis. Drug likeness of active compounds was also analyzed based on Lipinski's rule of five. Based on the drug likeness, active compounds (Baicalein, Epicatechin, Genistein, Quercetin, Resveratrol) were finally screened for molecular docking with CHIKV envelope proteins using Auto Dock program. Among the five active compounds, Genistein showed highest binding energy for both E1 (ΔG = - 8.3 kcal/mol) and E2 (ΔG = - 7.1 kcal/mol). Molecular dynamics simulations signify that Genistein forms a stable complex with the CHIKV E1 and E2 proteins over a 50 ns period with a significant number of hydrogen bonds. So this present study concluded that Genistein will act as potent CHIKV E1 and E2 inhibiting active compounds. To evaluate efficiency or inhibiting capacity of finally selected Genistein against CHIKV, in vivo and in vitro validation should be conducted.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00351-3.

Keywords: ADMET; Active compounds; CHIKV; Docking; Simulation.