Cytotoxicity, Antioxidant Activity, Molecular Docking, and Dynamics Simulation Analysis Against SARS-CoV-2 M and N Protein Models of Phytoconstituents of Micromelum Minutum

Abstract

Phytochemical investigations of the methanolic extract of the whole plant of Micromelum minutum provided two coumarins, namely micromelin and murrangatin, and one sterol stigmast-4-en-3-one, the latter being reported for the first time from M. minutum. To evaluate bioactivities, different fractions of the crude methanol extracts of the plant obtained by partitioning were screened for antioxidant and cytotoxic activity by DPPH radical scavenging method and the brine shrimp lethality bioassay, respectively. Among the different fractions of M. minutum tested, pet ether and chloroform soluble fractions showed prominent antioxidant activities with IC50 values of 49.46 and 67.53 μg/mL compared to the standard butylated hydroxytoluene (IC50 31.02 μg/ml). The pet ether and chloroform fractions of M. minutum showed good brine shrimp larvicidal activity with LC50 values of 1.15 and 1.50 μg/ml, respectively, compared to vincristine sulfate (LC50 0.27 μg/ml). The results obtained from molecular docking, Stigmast-4-en-3-one exerts the highest negative binding affinity (-9.1 kcal/mol) for interaction with SARS-CoV-2 M protein and develops a strong network with eleven hydrophobic bonds established by ADMET profile studies and YASARA Dynamics program.