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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Entrapment of flow of substrate to diversion pathway : strategy to combat persistent tuberculosis

The post genomic era has provided the leap into the quantitative biology and introduced biologists into the “omes” & “ics” world. For biologists it is utmost important to know the biology of disease and the mechanism of action of medicines. But no longer are these contained in the domain of physiology & medicinal chemistry. The importance of reorganizing our thinking process is mostly reflected in the merger & acquisition of Biotechnology, Bioinformatics and Chemoinformatics companies by/with large pharmaceutical companies recently.

The development in the field of molecular modeling and simulation has played the leading role in the drug design technology in pharmaceutical industry. Starting from Genomics, alignment of genes of interest amongst the species, three dimensional structure prediction from the knowledge of sequence of amino acids, prediction of active sites, searching for lead compounds using database and structure-based design, prediction of binding efficiency prior to the experiment and lead optimization using physico-chemical properties of the compounds are a few to cite. One such case study using in silico attempt towards the designing from known anti-tuberculosis chemicals a set of novel inhibitor and finding the drug target (s) using pathway simulation and analysis [1-3] will be discussed in brief.

Recent news has warned the medical community that war against pathogenic bacteria is yet not over, repeated breaking of different drug resistance in different range of pathogen has been observed in the patient especially in developing & underdeveloped countries. Many researchers, probably the next to cancer are experimentally using many prong attack on the understanding the mechanism and developing new strategy of inhibitors for combating this phenomena, resurging XDR,MDR,PDR. The extensive discussion to define these classes is available in literature [4-7]. Research work engaging with clinician, epidemiologist, biologists, microbiologist etc. in this field is emerging to highlight the complexity of the problem. However, many chemicals has been developed to combat the MDR/XDR Tb yet not been fully successful for a long time. Tuberculii , bacteria has shown to have multiple spontaneous mutations at a predictable rate and independent of different drug administration. Such phenomena are prevalent to many bacterial & more common to viral disease which leads researchers to develop multiple target drug designing.

Present discussion will open up the future of understanding of disease , its inter relationship within biochemical pathway & effect of protein-protein interaction identified as target for combating persistence stage in bacteria.

References

    1. Developing an Antituberculosis compounds database & data mining in the search of a motif responsible for the activity of a diverse class of Antituberculosis agents, Om Prakash & Indira Ghosh , Journal of Chemical Information and Modeling, 46, 17-23, 2006.

    2. Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets, Vivek Kumar Singh and Indira Ghosh , Theoretical Biology and Medical Modelling, BMC Journal. 3;3:27. 2006.

    3. Determination of Phosphorylation Sites for NADP-specific Isocitratedehydrogenase from Mycobacterium tuberculosis, Rithvik Vinekar &Indira Ghosh in Journal of Biomolecular Structure & Dynamics, Volume 26, Issue Number 6, p 663-895 ,2009.

    4. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance, A.-P. Magiorakos, et al, Clin Microbiol Infect. July 2011 , 10.1111/j.1469-0691.2011.03570.x

    5. Treatment of Multidrug-Resistant Tuberculosis, Michael D. Iseman, New Engl J Med 1993; 329:784-791September 9, 1993. 6. Multidrug-Resistant Tuberculosis and Culture Conversion with Bedaquiline , Andreas H. Diacon etal. New engl j med 371;8 nejm.org august 21, 2014.

    7. Drug-resistance mechanisms and tuberculosis drugs, Claudio U Köser etal, Lancet. 2015 January 24; 385(9965): 305–307. doi:10.1016/S0140-6736(14)62450-8.

Indira Ghosh

School of Computational & Integrative Sciences
Jawaharlal Nehru University
New Delhi, India