Identification of novel therapeutic target and epitopes through proteome mining from essential hypothetical proteins in Salmonella strains: An In silico approach towards antivirulence therapy and vaccine development
| Autor: | Pragati Prasad Sah, Sujay Ray, Arundhati Banerjee, Shreya Bhattacharya |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Proteomics 0301 basic medicine Microbiology (medical) Salmonella Protein Conformation Salmonella Vaccines Virulence Factors T-Lymphocytes In silico 030106 microbiology Druggability Virulence Computational biology Biology medicine.disease_cause Microbiology Epitope Epitopes 03 medical and health sciences Bacterial Proteins Genetics medicine Humans Computer Simulation Molecular Biology Ecology Evolution Behavior and Systematics B-Lymphocytes Salmonella enterica Salmonella vaccine Anti-Bacterial Agents 030104 developmental biology Infectious Diseases Membrane protein Drug Design Vaccines Subunit Proteome |
| Zdroj: | Infection, Genetics and Evolution. 83:104315 |
| ISSN: | 1567-1348 1032-0148 |
| DOI: | 10.1016/j.meegid.2020.104315 |
| Popis: | Salmonella strains are responsible for a huge mortality rate through foodborne ailment in the world that necessitated the discovery of novel drugs and vaccines. Essential hypothetical proteins (EHPs), whose structures and functions were previously unknown, could serve as potential therapeutic and vaccine targets. Antivirulence therapy shall emerge as a superior therapeutic approach that uses virulence factors as drug targets. This study annotated the biological functions of 96 out of total 106 essential hypothetical proteins in five strains of Salmonella and classified into nine important protein categories. 34 virulence factors were predicted among the EHPs, out of which, 11 were identified to be pathogen specific potential drug targets for antivirulence therapy. These targets were non-homologous to both human and gut microbiota proteome to avoid cross-reactivity with them. Seven identified targets had druggable property, while the rest four targets were novel targets. Four identified targets (DEG10320148, DEG10110027, DEG10110040 and DEG10110142) had antigenic properties and were further classified as: two membrane-bound Lipid-binding transmembrane proteins, a Zinc-binding membrane protein and an extracellular glycosylase. These targets could be potentially used for the development of subunit vaccines. The study further identified 11 highly conserved and exposed epitope sequences from these 4 vaccine targets. The three-dimensional structures of the vaccine targets were also elucidated along with highlighting the conformation of the epitopes. This study identified potential therapeutic targets for antivirulence therapy against Salmonella. It would therefore instigate in novel drug designing as well as provide important leads to new Salmonella vaccine development. |
| Databáze: | OpenAIRE |
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