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. 2025 May;22(5):e202402908.
doi: 10.1002/cbdv.202402908. Epub 2025 Jan 20.

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

Nneka Augustina Akwu  1   2 , Yougasphree Naidoo  1 , Moganavelli Singh  1 , Johnson Lin  1 , Jamiu Olaseni Aribisala  3 , Saheed Sabiu  3 , Makhotso Lekhooa  4 , Adeyemi Oladapo Aremu  1   2
Affiliations

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

Nneka Augustina Akwu et al. Chem Biodivers. 2025 May.

Abstract

The genus Grewia are well-known for their medicinal properties and are widely used in traditional remedies due to their rich phytochemical composition and potential health benefits. This study isolated and characterized five endophytic fungi from Grewia lasiocarpa E. Mey. Ex Harv. and evaluated their in vitro antibacterial and antioxidant activities. Five [Aspergillus fumigatus (MK243397.1), A. fumigatus (MK243451.1), Penicillium raistrickii (MK243492.1), P. spinulosum (MK243479.1), Meyerozyma guilliermondii (MK243634.1)] of the 22 isolated endophytic fungi had inhibitory activity (62.5-1000 µg/mL) against methicillin-resistant Staphylococcus aureus (MRSA). The antioxidant activities were 66.5% and 98.4% for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP), 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 docking and 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 optimization for improved druggability. Hence, isolating and derivatizing dehydroergosterol for subsequent evaluation against PBP2a in vitro and in vivo is highly recommended.

Keywords: Aspergillus sp; Meyerozyma guilliermondii; Penicillium sp; methicillin‐resistant Staphylococcus aureus; molecular docking; penicillin‐binding protein 2a (PBP2a).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Docking protocol validation via superimposition of the docked top‐hit compounds with the experimental native inhibitor at the active sites of 6H5O. The docked experimental inhibitor (black), reference standard amoxicillin (green), and top‐hit compounds [triphenyl phosphate (purple), ergosta‐4,6,8 (yellow), ergosterol (blue), β‐sitosterol (brown), and dehydroergosterol (red), 4‐azaphenanthrene (pink)] all had an RMSD of 3.0 Å from the experimental native inhibitor suggesting partial binding orientation of the docked compounds and the experimental native inhibitors.
FIGURE 2
FIGURE 2
(A–E) Morphology of the five endophytic fungi from the leaves and stem bark of Grewia lasiocarpa E. Mey. Ex Harv. with antibacterial activity. GLANA1 = Aspergillus fumigatus (MK243397.1), GLANA2 = Aspergillus fumigatus (MK243451.1), GLANA3 = Penicillium spinulosum (MK243479.1), GLANA4 = Penicillium raistrickii (MK243492.1) and GLANA5 = Meyerozyma guilliermondii (MK243634.1).
FIGURE 3
FIGURE 3
Overlay of the Fourier transform infrared spectroscopy (FTIR) spectra of the five‐bioactivity directed selected endophytic fungi from the leaves and stem bark of Grewia lasiocarpa E. Mey. Ex Harv. GLANA1 = Aspergillus fumigatus (MK243397.1), GLANA2 = Aspergillus fumigatus (MK243451.1), GLANA3 = Penicillium spinulosum (MK243479.1), GLANA4 = Penicillium raistrickii (MK243492.1) and GLANA5 = Meyerozyma guilliermondii (MK243634.1).
FIGURE 4
FIGURE 4
Phylogenetic tree depicting the genetic relationship between all five Aspergillus fumigatus (MK243397.1), Aspergillus fumigatus (MK243451.1), Penicillium spinulosum (MK243479.1), Penicillium raistrickii (MK243492.1) and Meyerozyma guilliermondii (MK243634.1) strains (GLANA1‐5) from this study and closely related fungal DNA sequences obtained from NCBI. Bootstrap consensus tree generated by Bootstrap test phylogeny using neighbour‐joining (N‐J) method of MEGA 7 Software.
FIGURE 5
FIGURE 5
Comparative root mean square deviation (RMSD) plots of the alpha‐carbon, the top six compounds, as well as the standard amoxicillin against the active site of penicillin‐binding protein 2a (PBP2a) of Staphylococcus aureus over a 100 ns molecular dynamic (MD) simulation period. These figures assess the stability of these top six compounds within the active site of PBP2a, compared to the reference standard and the alpha‐carbon of PBP2a itself. Overall, the comparison shows that all the compounds maintain stability with only minor fluctuations.
FIGURE 6
FIGURE 6
Comparative radius of gyration (ROG) plots of alpha‐carbon, the top six compounds and standard (amoxicillin) against the active site of penicillin‐binding protein 2a (PBP2a) of Staphylococcus aureus over 100 ns molecular dynamic (MD) simulation period. The figure reflects the overall compactness and folding of the PBP2a complexed with the top six compounds compared to that of the reference standard and the alpha‐carbon of PBP2a. Relative to the reference standard and the alpha‐carbon of PBP2a, all the complexes formed against PBP2a by the top six compounds were observed to be compact. Although other complexes were folding, amoxicillin‐complex (red) was unfolded especially between 15 and 100 ns of the simulation period.
FIGURE 7
FIGURE 7
Comparative root means square fluctuation (RMSF) plots of alpha‐carbon, the top six compounds, and standard, amoxicillin against residues of penicillin‐binding protein 2a (PBP2a) after 100 ns molecular dynamic (MD) simulation. The active site residues noted in Figure 1 were observed to be outside the region of higher residue fluctuations found before the 250 amino acid residues.
FIGURE 8
FIGURE 8
Comparative solvent‐accessible surface area (SASA) plots of alpha‐carbon, top six compounds and standard (amoxicillin) against the active site of penicillin‐binding protein 2a (PBP2a) of Staphylococcus aureus over 100 ns molecular dynamic (MD) simulation period. The figure reflects the overall compactness and folding of the PBP2a complexed with the top six compounds compared to that of the reference standard and the alpha‐carbon of PBP2a. Relative to the reference standard and the alpha‐carbon of PBP2a, all the complexes formed against PBP2a by the top six compounds were observed to be compact.
FIGURE 9
FIGURE 9
Time evolution of the number of intramolecular hydrogen bonds and distance in penicillin‐binding protein 2a (PBP2a) following the binding of the standard amoxicillin and the top six compounds at the active site of PBP2a of Staphylococcus aureus during the 100 ns molecular dynamic (MD) simulation period.
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