In-silico STUDY OF DITERPENOID LACTONES FROM Andrographis paniculate TO INTERLEUKIN-6 (IL-6) PROTEIN TARGET

Abstract

Interleukin-6 (IL-6) is a type of cytokine that is most often produced when there is inflammation of the respiratory system. Andrographolide, a diterpenoid lactone has been shown to inhibit the amount of IL-6 by binding to IL-6 receptors on human cells. This research was conducted to determine the other potential of diterpenoid lactones from Andrographis paniculate in inhibiting IL-6 with a computational chemistry approach method. The hexameric human IL-6 complex (1P9M) crystal structure was downloaded from the Protein Data Bank. The test compounds were built using MarvinSketch of ChemAxon and were subjected to energy minimization using the MMFF94 force field partial charges in the LigandScout software. Molecular Docking and Pharmacophore Modeling was carried out on an autodock algorithm that was embedded in Ligand Scout. The result showed that andrographolide has the best interaction with the IL-6 receptor with a binding affinity (Ei = -8.05 kcal/mol) and inhibition constant (Ki = 1.26 μM). Pharmacophore modeling of andrographolide in the IL-6 active site was validated against the training set of active ligands and decoys. The Pharmacophore features show the hydroxyl group on the C-14 atom acts as a hydrogen bond donor with Asn136 and hydrogen bond acceptor with Lys66. The hydroxyl group on the C-19 atom acts as a hydrogen bond acceptor with Leu57 and Ala58. Hydrophobic functional groups interact with Ala56, Leu62, Leu64, and Leu165. From the results of the study, it was concluded that andrographolide interacts well with the active site of IL-6, and has the potential to act as an IL-6 inhibitor that can prevent the release of cytokines that may be useful in the treatment of COVID-19.