Discovery of multitarget-directed small molecule inhibitors from Andrographis paniculata for Nipah virus disease therapy: Molecular docking, molecular dynamics simulation and ADME-Tox profiling

Abstract

Nipah virus (NiV), an emerging highly infectious agent, causes fatal infection to humans through zoonosis, particularly in Asian countries including India. No specific treatment or vaccine is available to cure or combat the NiV infection. Targetable plant-based computer-assisted drug discovery is a novel approach to combat NiV disease. The purpose of the current in silico study was to evaluate the potential of Andrographis paniculata phytochemicals to act as drug molecules to combat NiV disease by targeting multiple NiV proteins: attachment glycoprotein (NiV-G), nucleoprotein (NiV-N) and phosphoprotein (NiV-P). Six phytochemicals from A. paniculata: andrograpanin (AGNN), andrographidine E (AGDN), andrographin (AGPN), andrographolide (AGLD), deoxyandrographolide (DGLD) and neoandrographolide (NGLD) were docked against NiV-G, NiV-N and NiV-P. Outcomes of molecular docking approved the anti-NiV capacity of A. paniculata compounds with top binding affinity of NGLD against all the targets NiV-G, NiV-N and NiV-P with binding energies -8.1, -7.7 and -6.0 kcal/mol, respectively. The molecular dynamic simulation results further validated the protein-ligand docked complexes’ stability. Compared to the A. paniculata phytochemicals, standard antivirals, favipiravir and ribavirin, had low efficacy against all the target proteins. Furthermore, the A. paniculata phytocompounds displayed acceptable drug-likeness and ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) profiles. Overall, the present findings can be translated into preclinical and clinical investigations to inspect A. paniculata phytochemicals as mainstream drugs for NiV disease.