Anshul Tiwari

Choke Point Analysis with Subtractive Proteomic Approach for Insilico Identification of Potential Drug Targets in Shigella Dysenteriae

Shigellosis is an endemic disease prevalent in developing and poor countries due to fecal-oral transmission resulting a significant morbidity and mortality rate. Emergence of multidrug resistant (MDR) in Shigella sp. reveals the inefficacy towards the first line antibiotics like quinolones, cotrimoxazole and ampicillin against it. There is continuous need to monitor the characteristics and antibiotic resistance patterns of this pathogen regarding the identification of new potential therapeutic drug targets. Availability of complete protein of different Shigella species viz flexneri, body, dysentery and son has made it possible to carry out the Insilico analysis of its protein for the identification of potential vaccine and drug targets. Subtractive proteomics approach is being used to mine the list of proteins present in different Shigella species which are non-homologous to human and essential for the survival of the pathogen. The metabolic chokepoint analysis also enriches the list of essential protein and adds those proteins in the list which are uniquely found in pathogenic pathway, catalyzed by single enzyme and involved in multi pathways. Screening of essential proteins against human gut flora and approved drug targets revealed the targets which are non-homologous to human gut flora and homologous to the approved drug targets. Broad spectrum drug targets screening revealed a list of highly conserved proteins of various pathogens including different Shigella species. Probably the drug developed against these targets may be useful in treating multiple diseases or diseases which results due to co-infection of different pathogens. Subcellular localization prediction revealed a list protein, which could be potential vaccine targets in different Shigella species. Virtual screening against these identified targets might be useful in the discovery of novel Drug against MDR Shigella species.

Virtual Screening of Natural and Synthetic Ligands Against Diabetic Retinopathy by Molecular Interaction With Angiopoietin-2.

PurposeDiabetic retinopathy (DR) is the most common diabetic eye disease and a leading cause of blindness. The role of angiopoietin-2 a tyrosine kinase receptor is well-reported in angiogenesis during the onset of the disease. The purpose of this study is to screen out more potential herbal molecules which can evidently be used as a better, natural and safe herbal drug against this disease. DesignIn silico virtual screening and molecular interaction studies were performed. MethodsThe current course of work focused on molecular interactions on angiopoietin-2 protein with selected natural ligands, namely allicin, ajoene, D-pinitol and salacinol, along with synthetic ones like nateglinide, biguanide, tolbutamide and tolazamide. There was an attempt to carry out the virtual comparative study between natural and synthetic ligands. Proceeding toward this approach, docking of all molecules was performed using the Autodock 4.2 program. ResultsInference of this interaction study is that D-pinitol, which is the herbal extract of Glycine max, shows a very reliable docking pattern as compared with the synthetic ligand tolazamide. Although the binding energy of a synthetic ligand is lower compared to that of the natural ones, the binding energy of synthetic and natural ligands are at an approximate level. The lower the binding energy, the better the ligand molecular interaction. ConclusionsOur findings suggest that D-pinitol, the natural, safe ligand, can be used in the treatment of diabetic retinopathy with few or no side effects after estimating and calculating proper doses using in vitro approaches.

Bioinformatics in Retina.

Abstract Bioinformatics, a word coined for the applications of computer science in biology, is now promising as a major constituent in modern biology and biomedical research. Bioinformatics plays an important role for the integration of broad disciplines of biology to understand the complex mechanisms of the cell. Bioinformatics also aids the way in which biomedical investigators use the information in their testing. Development and implementation of this novel field enable efficient access and management of different types of biological information including those at the genomic, proteomic, and metabolomic level to understand about disease mechanisms and identify new molecular targets for drug discovery. Bioinformatics has expanded its wings in exploring out different important contributions in relation with medical sciences such as neurology, parasitology, hematology, and pathology including ophthalmology. Many bioinformatics-oriented studies have contributed a lot in ophthalmology and given birth to new avenues of occuloinformatics, hence, a new coined term, occuloinformatics: a new approach of research and diagnostics related to ocular disorders with significant inputs of bioinformatics. In this current review, we tried to focus on current avenues and significant contributions of bioinformatics with special reference to retinal disorders.

Phylogenetic analysis of poly and non structural protein in Japanese Encephalitis virus with other related viral families

Background Japanese encephalitis (JE) causes inflammation of brain. The mortality rate due to JE is 30% while 10 –15 % of patients make full recovery. The disease spreads through infected mosquito bites breeding in rice fields and feeds on pigs, birds, and ducks. Purpose As proteins show important structure to function relationship the study was designed to carry out the identification of poly and non–structural proteins in the infective virus group using different strains of Japanese encephalitis virus i.e. JAOARS982, Nakayama Strain SA (V), Strain SA–14. Methods With reference to non structural proteins we obtained protein sequences of the following Japanese encephalitis virus groups: Japanese encephalitis virus, Weatnile virus, Kunjin virus. Further comparative and phylogenetic analysis was performed to explore evolutionary relationship among these groups. Results Results of phylogeny of alignment score was found to be 375184 using multiple alignment, Jal view, ClustalW (1.83) and ClustalW2. However, the analysis among the non–structural proteins of Japanese Encephalitis Virus, Westnile Virus, and Kunjin Virus revealed the phylogeny alignment score to be 875 through multiple sequence alignment and Tree view respectively. Conclusion Phylogenetic analysis revealed that these four strains are interrelated as well as showing high similarity with the other viruses of this group due to conserved regions among their sequences.