SCREENING OF PUTATIVE THERAPEUTIC CANDIDATES IN SUPERBUG (STAPHYLOCOCCUS AUREUS): A SYSTEMATIC IN SILICO APPROACH

ABSTRACTObjective: Staphylococcus aureus, a superbug and antibiotic resistant pathogen, is one of the most infection causing organism, ranging from skinallergies to severe lethal conditions. The prolonged use of different antibiotics and lack of optimal treatment over the antibiotic resistant species, ledto the identification of new, better and promising therapeutic candidates. Methods: A systematic in silico filtration process was employed, which includes subtractive channels and reverse vaccinology techniques. Results: Here, we report 12 possible drug targets and two vaccine candidates based on essentiality, non-human homolog, virulent and localization,commonly in all the strains. Further characterization studies such as pathway analysis, chokepoint and structure prediction revealed, two proteinsas the best drug targets one being novel and the other druggable. Only one protein has shown the characteristic feature of vaccine candidate, havingantigenic property and an IgG binding domain. Conclusion: Two best drug targets were commonly identified in all the strains of S. aureus namely UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysineligase (MurE) and cell division protein FtsA, whereas the best common vaccine candidate includes Peptidoglycan binding protein. The therapeutic candidatesreported in the present study might facilitate screening of new and better antimicrobial compounds, for an optimal treatment of S. aureus infections.Keywords: Staphylococcus aureus, Drug target, Vaccine candidates, Subtractive proteomics, Reverse vaccinology

PREDICTION OF PROMISCUOUS EPITOPE STUDIES OF SPA ANTIGEN IN STAPHYLOCOCCUS AUREUS: AN INSIGHT ON PEPTIDE-BASED VACCINE

Objective: Owing to the difficulty in providing drug therapies against Methicillin-resistant Staphylococcus aureus (MRSA), the development of an effective and promising vaccine is an immense challenge in combatingMRSA infections. The present work focuses on the development of a peptide-based vaccine, by identifying the epitopes from SPA antigen.Methods: The epitopes were identified based on different properties, such that they are capable of eliciting broadly neutralizing immune responses. The identified epitopes were subjected for peptide docking using Glide and antibody-antigen docking using ClusPro.Results: By in silico approach two epitopes NLNEEQRNG†and LKDDPSQSAN†were identified for SPA protein with sequence lengths of nine and ten respectively. The least energy for the peptide docking was observed for NLNEEQRNG sequence and the amino acid residues of this peptide share similar interaction with antibody-antigen docking.Conclusion: Based on the properties and docking studies the best-ranked epitope sequence is ‘NLNEEQRNG'. Further studies on this peptide sequence might be helpful for alternative therapy of MRSA infections.Keywords: Epitope, SPA antigen, IgG antibody, Docking studie

Insilico Proteome Screening to Identify Prospective Drug Targets in Bacillus anthracis

Various Insilico based genome screening methods helped us in identifying the key drug targets for  a pathogen. The accuracy of the predictions are systematically based on the benchmarks at different stages of methodology and the kind of dataset which is considered for the study. In the current study, we made an effort to screen the entire proteome of Bacillus anthracis for identification of putative drug targets. B. anthracis is the causautive agent for anthrax disease. Instead of genome sequence, the metabolically classified proteome of B. anthracis from JCVI-CMR database was considered for the present study. The entire proteome is been categorized into 25 different metabolisms and in each sub-categorised metabolisms respective protein sequences were retrieved and subjected to screening against Database of Essential Genes (DEG) and Human-Basic Local Alignment Search Tool (H-BLAST) databases. In total 136 essential genes/proteins were obtained from the DEGp (protein) screening whereas 145 Non-Human Homologs (NHHs) were predicted. The identified 145 NHHs are further subjected to criteria based selection to identify the most suitable, functional, putative drug targets. The 8 common hits of both DEG and H-BLAST were considered to be better potential targets as they justify the criteria of being an essential gene/protein, non-human homolog, availability of the 3D structure in PDB and having a significant functional role in the cellular biochemical processes.