ABSTRACT
Bignoniaceae plants are multipurpose herbal remedies with privileged chemical and biological profiles;nevertheless, some members in this family, e.g. Amphilophium species, have been scarcely investigated. Therefore, this work explores the chemical complexity of the underexplored species, Amphilophium paniculatum (L.) Kunth as a potential source of inhibitory phytochemicals against the recently emerging coronavirus disease (COVID-19). Overall, 13 structurally varied metabolites were isolated from the ethyl acetate and n-butanol fractions of A. paniculatum leaves for the first time in the genus and identified by different spectral techniques, including H-1 and C-13 NMR, DEPT, and HR-ESI-MS analyses. The characterized compounds (1-13), along with those previously obtained by our group from the same species (14-22) revealed varying binding affinities to the active site of SARS-CoV-2 M-pro, among which, eight molecules exhibited lower binding energies (-9.54 to -7.45 kcal/mol) than the ligand N3 (-7.44 kcal/mol);with polyphenolic metabolites, namely flavonoids, phenylethanoids, and lignans had the most stable interactions, respectively. These results highlighted the noteworthy diversity of A. paniculatum metabolites and their marked homogeneity with those produced by other Bignoniaceae plants, which would help expand our phytochemical and chemotaxonomic knowledge on this species. Coupling such phytochemical data with molecular docking studies could also allow a time- and cost-effective search for potential anti-COVID-19 agents. (C) 2021 SAAB. Published by Elsevier B.V. All rights reserved.
ABSTRACT
AIMS: To identify the metabolites produced by the endophytic fungus, Aspergillus terreus and to explore the anti-viral activity of the identified metabolites against the pandemic disease COVID-19 in-silico. METHODS AND RESULTS: Herein, we reported the isolation of A. terreus, the endophytic fungus associated with soybean roots, which is then subcultured using OSMAC approach in five different culture media. Analytical analysis of media ethylacetate extracts using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was carried out. Furthermore, the obtained LC-MS data were statistically processed with MetaboAnalyst 4.0. Molecular docking studies were performed for the dereplicated metabolites against COVID-19 main protease (Mpro ). Metabolomic profiling revealed the presence of 18 compounds belonging to different chemical classes. Quinones, polyketides and isocoumarins were the most abundant classes. Multivariate analysis revealed that potato dextrose broth and modified potato dextrose broth are the optimal media for metabolites production. Molecular docking studies declared that the metabolites, Aspergillide B1 and 3a-Hydroxy-3, 5-dihydromonacolin L showed the highest binding energy scores towards COVID-19 main protease (Mpro ) (-9·473) and (-9·386), respectively, and they interact strongly with the catalytic dyad (His41 and Cys145) amino acid residues of Mpro . CONCLUSIONS: A combination of metabolomics and in-silico approaches have allowed a shorter route to search for anti-COVID-19 natural products in a shorter time. The dereplicated metabolites, aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L were found to be potent anti-COVID-19 drug candidates in the molecular docking study. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the endophytic fungus, A. terreus can be considered as a potential source of natural bioactive products. In addition to, the possibility of developing the metabolites, aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L to be used as phytopharmaceuticals for the management of COVID-19.