IJMS, Vol. 26, Pages 6480: Potent Inhibition of Chikungunya Virus Entry by a Pyrazole–Benzene Derivative: A Computational Study Targeting the E1–E2 Glycoprotein Complex

International Journal of Molecular Sciences doi: 10.3390/ijms26136480

Authors:
Md. Mohibur Rahman
Md. Belayet Hasan Limon
Tanvir Ahmed Saikat
Poulomi Saha
Abdul Hadi Nahid
Mohammad Mamun Alam
Mohammed Ziaur Rahman

The Chikungunya virus (CHIKV) continues to pose a significant global health challenge due to the absence of effective antiviral treatments and limited vaccine availability. This study employed a comprehensive in silico workflow, incorporating high-throughput virtual screening, binding free-energy calculations, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, and 200 ns molecular dynamics (MD) simulations, to identify new inhibitors targeting the E1–E2 glycoprotein complex, crucial for CHIKV entry and membrane fusion. Four promising candidates were identified from a library of 20,000 compounds, with CID 136801451 showing the most potent binding (docking score: −10.227; ΔG_bind: −51.53 kcal/mol). The top four compounds exhibited favorable ADMET profiles, meeting nearly all criteria. MD simulations confirmed stable binding and strong interactions between CID 136801451 and the E1–E2 complex, evidenced by consistently low RMSD values. These findings highlight CID 136801451 as a promising CHIKV entry inhibitor, warranting further in vitro and in vivo evaluation to advance the development of effective anti-CHIKV therapeutics.

Source link

Md. Mohibur Rahman www.mdpi.com