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.
Subject(s)
Aspergillus , COVID-19 , Molecular Docking Simulation , Glycine max , Aspergillus/metabolism , COVID-19/therapy , Computer Simulation , Fungi , Humans , Metabolomics , SARS-CoV-2ABSTRACT
Natural polyphenolic drugs were approved for treatment of various diseases. Diosmin, rutin, quercetin, aesculin, genistein, hesperidin and silybin are known for their safety and have been applied for several human disorders including cancer, cardiovascular disorders, atherosclerosis, oxidative stress, capillary fragility, liver and pancreatic disorders and others. As the structures of the selected polyphenolic compounds possess variable chemical moieties with diverse chemical and electronic characters, these properties have been employed for further insights studies to predict new applications concerning the newly occurred pandemic. COVID-19 is a terrible disease that attacked millions of human populations at the end of year 2019. As the number of death cases has increased to exceed one million of humans, the early discovery of new treatment from previously approved and safe drugs is the main target of this study. Employing the putative docking studies for the selected polypheno-lic drugs were done and the results were promising, all tested drugs exhibited high affinity with the selected five proteins of protease enzyme, the docking score ranged from-8.4461 to-26.1691 kcal/mol with 3-7 variable interaction bonds. Among the tested drugs, diosmin appeared as the most promising drug as it exhibited the highest energy score and interaction bonds with the most of proteins.