Structural basis for complementary and alternative medicine: Phytochemical interaction with non-structural protein 2 protease-a reverse engineering strategy

To understand the druggability of the bioactive compounds from traditional herbal formulations Nilavembu Kudineer and Swasthya Raksha Amruta Peya to heal chikungunya virus (CHIKV) infection. The efficiency of twenty novel chemical entities from Nilavembu Kudineer and Swasthya Raksha Amruta Peya to inhibit CHIKV infection in silico were evaluated. Ligands were prepared using Ligprep module of Schrodinger. Active site was identified using SiteMap program. Grid box was generated using receptor grid generation wizard. Molecular docking was carried out using Grid Based Ligand Docking with Energetics (GLIDE) program. Molecular docking studies showed that among twenty compounds, andrographoside, deoxyandrographoside, neoandrographolide, 14-deoxy-11-oxoandrographolide, butoxone and oleanolic acid showed GLIDE extra precision (XP) score of -9.10, -8.72, -8.25, -7.38, -7.28 and -7.01, respectively which were greater than or comparable with chloroquine (reference compound) XP score (-7.08) and were found to interact with the key residues GLU 1043, LYS 1045, GLY 1176, LEU 1203, HIS 1222 and LYS 1239 which were characteristic functional unit crucial for replication of CHIKV. The binding affinity and the binding mode of chemical entities taken from herbal formulations with non-structural protein 2 protease were understood and our study provided a novel strategy in the development and design of drugs for CHIKV infection.