Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of coronavirus disease 2019 (COVID-19), has caused serious health problems worldwide and placed tremendous socioeconomic burdens. Azadirachta indica (Neem) is known as a versatile medicinal plant with many pharmacology activities. This study explored the potency of bioactive compounds from A. indica as inhibitors for SARS-CoV-2 main protease (Mpro) through molecular docking and molecular dynamics simulation (MDS) studies. Molecular docking and MDS were performed on 76 compounds contained in A. indica after a geometry optimization stage. This study found that odoratone (ORN), salimuzzalin (SMZ), and nimbocidin2 (NC2) had the best docking scores of −11.57, −9.83, and −9.60 kcal/mol, respectively. These scores are even better than nirmatrelvir (NTV) as an active drug targeting SARS-CoV-2 Mpro (−8.42 kcal/mol) and the reference ligand (FJC) (−7.93 kcal/mol). Although SMZ indicated the lowest average root mean square deviation value (1.90 Å) for the SARS-CoV-2 Mpro backbone disruption and the lowest average root mean square fluctuation value (1.32 Å) when interacting with residues, ORN still had the best average ΔGoMMGBSA value (−31.27 kcal/mol), which showed the strongest binding of the protein-ligand complexes. These results could be a starting point for further in vitro and in vivo evaluation of several compounds in A. indica that are potential SARS-CoV-2 Mpro inhibitors.
Key words: antiviral, Azadirachta indica, molecular docking, molecular dynamics simulation, SARS-CoV-2 main protease
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