Bioactive potentiality of secondary metabolites from endophytic bacteria against SARS-COV-2: An in-silico approach

Abstract

Five endophytic bacterial isolates were studied to identify morphologically and biochemically, according to established protocols and further confirmed by 16S rDNA Sanger sequencing, as Priestia megaterium, Staphylococcus caprae, Neobacillus drentensis, Micrococcus yunnanensis, and Sphingomonas paucimobiliz, which were then tested for phytohormone, ammonia, and hydrolytic enzyme production. Antioxidant compounds total phenolic content (TPC), and total flavonoid content (TFC) were assessed by using bacterial crude extracts obtained from 24-hour shake-flask culture. Phylogenetic tree analysis of those identified isolates shared sequence similarities with the members of Bacillus, Micrococcus, Staphylococcus, and Pseudomonas species, and after GenBank submission, accession numbers for the nucleotide sequences were found to be MW494406, MW494408, MW494401, MW494402, and MZ021340, respectively. In silico analysis was performed to identify their bioactive genes and compounds in the context of bioactive secondary metabolite production with medicinal value, where nine significant bioactive compounds according to six different types of bioactive secondary metabolites were identified, and their structures, gene associations, and protein-protein networks were analyzed by different computational tools and servers, which were reported earlier with their antimicrobial, anti-infective, antioxidant, and anti-cancer capabilities. These compounds were then docked to the 3-chymotrypsin-like protease (3CLpro) of the novel SARS-COV-2. Docking scores were then compared with 3CLpro reference inhibitor (lopinavir), and docked compounds were further subjected to ADMET and drug-likeness analyses. Ligand-protein interactions showed that two compounds (microansamycin and aureusimine) interacted favorably with coronavirus 3CLpro. Besides, in silico analysis, we also performed NMR for metabolite detection whereas three metabolites (microansamycin, aureusimine, and stenothricin) were confirmed from the 1H NMR profiles. As a consequence, the metabolites found from NMR data aligned with our in-silico analysis that carries a significant outcome of this research. Finally, Endophytic bacteria collected from medicinal plants can provide new leading bioactive compounds against target proteins of SARS-COV-2, which could be an effective approach to accelerate drug innovation and development.

De novo Genome Assessment of Serratia marcescens SGT5.3, a Potential Plant Growth-Promoting Bacterium Isolated from the Surface of Capsicum annuum Fruit

“…Functional annotation detected genes related to growth promotion ( glnH , glnG , nirB , nirD , and narK ), IAA phytohormones ( trpA , trpB , trpCF , and trpD ), cytokinins ( mia A and mia B), and a siderophore ( entS , entF , feoB , fetB , and fhuA ), among others; these genes are likely to be associated with plant growth promotion and development ( 13 – 15 ). The findings demonstrate the genetic capability of strain SGT5.3 for bioprospecting applications in agriculture.…”

Secondary Metabolites Produced by Plant Growth-Promoting Bacterial Endophytes

“…have been reported for their potent antimicrobial activities [ 89 ]. Additionally, bacteria belonging to the genera Staphylococcus, Micrococcus and Sphingomonas have been shown to have these genes, indicating a more universal distribution of these domains as suitable targets in endophytes where secondary metabolite discovery has substantial potential [ 98 ]. Furthermore, characterization of bacterial endophytes of thirty Chinese medicinal herbs on the basis of PKS and NRPS gene clusters suggested the production of known and unknown metabolites with putative bioactivities [ 99 ].…”

“…Thus, S. caprae may be a potential source of flavonoids for further studies of their anti-viral activity. Additional investigations through molecular docking experiments revealed the presence of two important metabolites, microansamycin and aureusimine, which displayed noteworthy activity against SARS-CoV-2 by altering the viral protease function, thus identifying the possible mode of action by which these extracts can help fight such infections [ 98 ].…”

Antioxidant and Antibacterial Activity of Endophytic Fungi Isolated from The Leaves of Sungkai (Peronema canescens)

“…[32][33][34][35][36] The secondary metabolites of these endophytic fungi are believed to be the most relevant discoveries for new medicinal materials. [37][38][39] They have the potential to overcome the synthetic © 2023 the authors. This work is licensed under the Creative Commons Attribution 4.0 International License antibiotics and antioxidants that have been used until today.…”