Exploring Centella asiatica-derived Compounds as Inhibitors of Chikungunya Virus nsP2 Protease: Insights into Pharmacokinetics Prediction
Abstract
Chikungunya virus (CHIKV) infection poses a significant global health threat, with limited treatment options. Objective: This study explores the potential of flavonoids, terpenoid, and triterpenoid compounds derived from Centella asiatica to inhibit the CHIKV nsP2 protease, a crucial enzyme in viral replication. Method: Through computational modelling, we demonstrate the inhibitory activity of these compounds against the nsP2 protease, highlighting their potential as therapeutic agents against CHIKV. Results: The results indicate that flavonoid derivatives from Centella asiatica, including castilliferol and castillicetin, exhibit lower binding energy values (-10 and -9.9, respectively) compared to the FDA drug emetine. Additionally, these flavonoid derivatives demonstrate specific inhibition of Lys1045 and Lys1239, active sites of the CHIKV nsP2 protease. Pharmacokinetic predictions provide valuable insights into the compounds’ absorption, distribution, metabolism, and excretion. This indicated that castilliferol and castillicetin fulfil Lipinski’s rule parameters in terms of physicochemical and ADMET properties.