Structural basis for complementary and alternative medicine: Phytochemical interaction with non-structural protein 2...

Area of Science:

• Pharmacology and Computational Chemistry
• Virology and Drug Discovery

Background:

• Traditional herbal formulations like Nilavembu Kudineer and Swasthya Raksha Amruta Peya are used in ethnomedicine.
• Chikungunya virus (CHIKV) infection poses a significant global health challenge with limited therapeutic options.

Purpose of the Study:

• To investigate the potential of bioactive compounds from Nilavembu Kudineer and Swasthya Raksha Amruta Peya as CHIKV inhibitors.
• To assess the druggability of these natural compounds through in silico methods.

Main Methods:

• In silico evaluation of twenty novel chemical entities from herbal formulations for CHIKV inhibition.
• Preparation of ligands using Schrödinger's Ligprep module and active site identification with SiteMap.
• Molecular docking simulations using the Grid Based Ligand Docking with Energetics (GLIDE) program.

Main Results:

• Six compounds, including andrographoside and oleanolic acid, exhibited strong binding affinity to CHIKV non-structural protein 2 protease.
• These compounds demonstrated binding scores comparable to or better than the reference drug chloroquine.
• Key interactions with essential residues (GLU 1043, LYS 1045, GLY 1176, LEU 1203, HIS 1222, LYS 1239) crucial for CHIKV replication were identified.

Conclusions:

• The study elucidated the binding affinity and mode of action of herbal compounds against CHIKV.
• These findings offer a novel strategy for developing new antiviral drugs against chikungunya virus infection.