Phytochemistry, Antibacterial and Antioxidant Activities of Grewia lasiocarpa E. Mey. ex Harv. Fungal Endophytes: A Computational and Experimental Validation Study.

The genus Grewia are known for their medicinal properties. We isolated and characterized five endophytic fungi from Grewialasiocarpa for in vitro antibacterial and antioxidant activities. Five [Aspergillus fumigatus (MK243397.1), Aspergillus fumigatus (MK243451.1), Penicillium raistrickii (MK243492.1), Penicillium spinulosum (MK243479.1), Meyerozyma guilliermondii (MK243634.1)] had inhibitory activity (62.5-1000 µg/mL) against methicillin-resistant Staphylococcus aureus (MRSA). Antioxidant responses were 66.5 and 98.4% for 2,2-diphenyl-1-picrylhydrazyl and Ferric Ion Reducing Antioxidant Power, respectively. In silico evaluation of the phytochemicals of the extract (containing majorly n-hexadecanoic acid) was performed against penicillin-binding protein 2a (PBP2a) implicated in the broad clinical resistance of MRSA to conventional beta-lactams. Molecular dynamic simulation analyses revealed that the phytosterol constituents of the extract, especially dehydroergosterol (- 46.28 kcal/mol) had good stability (4.35 Å), and compactness (35.08 Å) with PBP2a relative to the unbound PBP2a and amoxicillin-PBP2a complex during the 100 ns simulation period, reinforcing them as putative leads that may be developed as viable alternatives to beta-lactams against infections caused by MRSA. However, the prediction that dehydroergosterol lacks oral bioavailability with poor water solubility suggests that it could benefit from structural optimisation for improved druggability. Hence, isolating and derivatizing dehydroergosterol for subsequent evaluation against PBP2a in vitro and in vivo, is recommended.
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