title: Secondary metabolites extracted from marine sponge associated Comamonas testosteroni and Citrobacter freundii as potential antimicrobials against MDR pathogens and hypothetical leads for VP40 matrix protein of Ebola virus: an in vitro and in silico investigation.
abstract: The current study explores therapeutic potential of metabolites extracted from marine sponge (Cliona sp.)-associated bacteria against MDR pathogens and predicts the binding prospective of probable lead molecules against VP40 target of Ebola virus. The metabolite-producing bacteria were characterized by agar overlay assay and as per the protocols in Bergey's manual of determinative bacteriology. The antibacterial activities of extracted metabolites were tested against clinical pathogens by well-diffusion assay. The selected metabolite producers were characterized by 16S rDNA sequencing. Chemical screening and Fourier Transform Infrared (FTIR) analysis for selected compounds were performed. The probable lead molecules present in the metabolites were hypothesized based on proximate analysis, FTIR data, and literature survey. The drug-like properties and binding potential of lead molecules against VP40 target of Ebola virus were hypothesized by computational virtual screening and molecular docking. The current study demonstrated that clear zones around bacterial colonies in agar overlay assay. Antibiotic sensitivity profiling demonstrated that the clinical isolates were multi-drug resistant, however; most of them showed sensitivity to secondary metabolites (MIC-15 μl/well). The proximate and FTIR analysis suggested that probable metabolites belonged to alkaloids with O-H, C-H, C=O, and N-H groups. 16S rDNA characterization of selected metabolite producers demonstrated that 96% and 99% sequence identity to Comamonas testosteroni and Citrobacter freundii, respectively. The docking studies suggested that molecules such as Gymnastatin, Sorbicillactone, Marizomib, and Daryamide can designed as probable lead candidates against VP40 target of Ebola virus.
authors.affiliation: a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India.
authors.forename: Sinosh
authors.initials: S
authors.lastname: Skariyachan
authors.affiliation: a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India.
authors.forename: Archana B
authors.initials: AB
authors.lastname: Acharya
authors.affiliation: a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India.
authors.forename: Saumya
authors.initials: S
authors.lastname: Subramaniyan
authors.affiliation: a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India.
authors.forename: Sumangala
authors.initials: S
authors.lastname: Babu
authors.affiliation: b Visvesvaraya Technological University , Belagavi , India.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Kulkarni
authors.affiliation: a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India.
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Narayanappa
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D016971:Citrobacter freundii / Q000145:classification / Q000187:drug effects / Q000235:genetics; D020604:Comamonas testosteroni / Q000145:classification / Q000187:drug effects / Q000235:genetics; D003198:Computer Simulation; D055808:Drug Discovery; D029043:Ebolavirus; D008024:Ligands; D055432:Metabolomics / Q000379:methods; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010802:Phylogeny; D011161:Porifera / Q000737:chemistry* / Q000378:metabolism / Q000382:microbiology*; D011485:Protein Binding; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D064210:Secondary Metabolism; D013559:Symbiosis; D014020:Tissue Extracts / Q000737:chemistry* / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D008024:Ligands; D012336:RNA, Ribosomal, 16S; D014020:Tissue Extracts; C080981:VP40 protein, virus; D014763:Viral Matrix Proteins
keywords: 16S rDNA sequencing; Cliona sp; Ebola virus; VP40 targets; computational virtual screening; marine sponges; molecular docking; multi-drug resistant; secondary metabolites