Soybean‐associated endophytic fungi as potential source for anti‐COVID‐19 metabolites supported by docking analysis

Abstract

Aims: to identify the metabolites produced by the endophytic fungus, Aspergillus terreus and to explore the antiviral activity of the identified metabolites against the pandemic disease COVID-19 insilico. Methods and results: herein, we reported the isolation of Aspergillus terreus, the endophytic fungus associated with soybean roots, which is then sub-cultured using OSMAC approach in five different culture media. Analytical analysis of media ethylacetate extracts using liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS) 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 (M pro). Metabolomic profiling revealed the presence of eighteen compounds belonging to different chemical classes. Quinones, polyketides and isocoumarins were the most abundant classes. Multivariate analysis Accepted Article This article is protected by copyright. All rights reserved 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 (M pro) (-9.473) and (-9.386), respectively, and they interact strongly with the catalytic dyad (His41 and Cys145) amino acid residues of M pro. 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, Aspergillus terreus can be considered as a potential source of natural bioactive products. In addition to, the potential of Aspergillide B1 and 3α-Hydroxy-3, 5-dihydromonacolin L to be developed as phytopharmaceuticals for the management of COVID 19.

Structure-Function Characteristics of SARS-CoV-2 Proteases and Their Potential Inhibitors from Microbial Sources

“…While the antibiotic is grouped under primary metabolite compounds, bacteriocin bacteriocins are ribosomally synthesized and produced during the primary phase of growth [107]. 11a-dehydroxyisoterreulactone A Molecular docking using UCSF Chimera, molecular dynamics using Amber 18, computational prediction of the absorption, distribution, metabolism, and excretion (ADME) properties using SwissADME software −8.9 [110] Aspergillide B1 Molecular docking using OpenEye's FRED −9.473 [111] Citriquinochroman Pharmacophore-based virtual screening using Pharmit molecular docking Autodock Vina −14.7 [108] Microorganisms 2021, 9, x 14 of 27…”

“…11a-dehydroxyisoterreulactone A Molecular docking using UCSF Chimera, molecular dynamics using Amber 18, computational prediction of the absorption, distribution, metabolism, and excretion (ADME) properties using SwissADME software −8.9 [110] Aspergillide B1 Molecular docking using OpenEye's FRED −9.473 [111] 11adehydroxyisoterreulactone A Molecular docking using UCSF Chimera, molecular dynamics using Amber 18, computational prediction of the absorption, distribution, metabolism, and excretion (ADME) properties using SwissADME software −8.9 [110] Microorganisms 2021, 9, x 14 of 27…”

“…11a-dehydroxyisoterreulactone A Molecular docking using UCSF Chimera, molecular dynamics using Amber 18, computational prediction of the absorption, distribution, metabolism, and excretion (ADME) properties using SwissADME software −8.9 [110] Aspergillide B1 Molecular docking using OpenEye's FRED −9.473 [111] Aspergillide B1 Molecular docking using OpenEye's FRED −9.473 [111] Microorganisms 2021, 9, x 15 of 27 3α-Hydroxy-3,5-dihydromonacolin L Molecular docking using OpenEye's FRED −9.386 [111] Sterenin M Molecular docking using Glide, ADMET analysis pkCSM-pharmacokinetics server, molecular dynamics using Desmond −8.431 [112] Hexadecanoic acid Molecular docking using AutoDock, molecular dynamics using Amber 18 −6.9 Sterenin M Molecular docking using Glide, ADMET analysis pkCSM-pharmacokinetics server, molecular dynamics using Desmond −8.431 [112] Hexadecanoic acid Molecular docking using AutoDock, molecular dynamics using Amber 18 −6.9 Sterenin M Molecular docking using Glide, ADMET analysis pkCSM-pharmacokinetics server, molecular dynamics using Desmond −8.431 [112] Microorganisms 2021, 9, x 15 of 27 3α-Hydroxy-3,5-dihydromonacolin L Molecular docking using OpenEye's FRED −9.386 [111] Sterenin M Molecular docking using Glide, ADMET analysis pkCSM-pharmacokinetics server, molecular dynamics using Desmond −8.431 [112] Hexadecanoic acid Molecular docking using AutoDock, molecular dynamics using Amber 18 −6.9 Hexadecanoic acid Molecular docking using AutoDock, molecular dynamics using Amber 18 −6.9 [113] Microorganisms 2021, 9, x 15 of 27 3α-Hydroxy-3,5-dihydromonacolin L Molecular docking using OpenEye's FRED −9.386 [111] Sterenin M Molecular docking using Glide, ADMET analysis pkCSM-pharmacokinetics server, molecular dynamics using Desmond −8.431 [112] Hexadecanoic acid Molecular docking using AutoDock, molecular dynamics using Amber 18 −6.9 Sterenin M Molecular docking using Glide, ADMET analysis pkCSM-pharmacokinetics server, molecular dynamics using Desmond −8.431 [112] Hexadecanoic acid Molecular docking using AutoDock, molecular dynamics using Amber 18 −6.9…”

“…By taking almost similar computational approaches, a study by El-Hawary et al [111] identified aspergillide B1 and 3a-hydroxy-3, and 5-dihydromonacolin L, and noted that they can interact with catalytic dyad (His41 and Cys145) amino acid residues of 3CLpro-CoV2. These metabolites are produced by the endophytic fungus, Aspergillus terreus, which is a similar microbe to Quimque et al [110].…”

Targeting 3CLpro and SARS-CoV-2 RdRp by Amphimedon sp. Metabolites: A Computational Study

“…Global health concerns have been raised by the COVID-19 pandemic [ 2 ], which has necessitated the search for drug candidates to help reduce its consequences. Certain natural products have been reported to act as potent drugs against COVID-19 [ 4 , 5 , 6 , 7 , 8 , 9 ]. Marine sponges are considered great reservoirs for potent antiviral chemicals [ 10 , 11 , 12 , 13 ].…”