Department of Life Sciences

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http://presiuniv.ndl.gov.in:4009/handle/123456789/2326

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Browsing Department of Life Sciences by Author "Giri, Kalyan"

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    In vitro propagation and phytochemical screening of three important ethno-medico-botanicals used by the ethnic communities of Purulia district, West Bengal, India
    Giri, Kalyan
    Background: In order to explore the traditional medicine practised by the ethnic communities residing in the Purulia district of West Bengal, India, a quantitative ethnobiological approach was adopted. Three medicinal plants viz. Bacopa monnieri, Aristolochia indica and Rauvolfia serpentina were selected, micropropagted, assessed for clonal fidelity and phytochemical markers. Materials and methods: Ethnobiological surveys were conducted by interviewing a number of informants or traditional healers with the help of a semi-structured questionnaire. The survey included questions on botanical ingredients and additives, vernacular names of the plants and animals, methods of preparation and administration and restrictions during medications. Additional quantitative indices such as use value, informant’s consensus factor and fidelity level were used for data analysis. On the basis of use value three plants viz. B. monnieri, A. indica and R. sepentina were selected and micropropagted in presence of various plant growth regulators (PGRs) and/or polyamines (PAs). Clonal fidelity of the three micropropagated plants were assessed by RAPD and ISSR based markers. Further, the plants were analyzed by validated HPTLC methods for the presence of marker compounds such as bacoside A, aristolochic acid I, reserpine, ajmalicine and stigmasterol. Results: A number of folkloric use of botanicals were reported by the traditional healers. High frequency in-vitro multiplication and regeneration in the three selected plants were achieved via use of PGRs and/or PAs. Clonal fidelity assessment of micropropagated plants using two markers (RAPD and ISSR) systems revealed high genetic homogeneity and low level of polymorphism. Comparative HPTLC analysis of bacoside A, aristolochic acid I and reserpine, ajmalicine and stigmasterol content in natural and in-vitro grown B. monnieri, A. indica and R. serpentina respectively indicated higher concentrations of bioactive phytochemicals in tissue-culture raised plants. Conclusion: Possible synergistic interactions among phytochemicals and additives were indicated to explain enhanced therapeutic efficacy of mixed herbal formulations. Moreover, in-vitro high frequency multiplication and regeneration from various explants may serve as exciting culture material for propagation and conservation of this valuable medicinal plant. HPTLC studies clearly indicated that in-vitro raised plant samples can be used as excellent resource for qualitative and quantitative estimation of high value pharmaceuticals.
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    Studies on the conformational dynamics of HIV-1 accessory proteins to guide new therapeutic development
    Giri, Kalyan
    The HIV-1 accessory proteins (Vpr, Vif, Vpu, and Nef) are multifunctional proteins that play a critical role in the virus progression and contributing to AIDS pathogenesis. These proteins engage with numerous host cellular proteins to execute various functions, promoting viral replication. These proteins show remarkable conformational plasticity i.e. they frequently undergo substantial structural changes upon binding to their targets. In this research, conformational dynamics of these proteins are thoroughly investigated thorough integrated computational modelling and molecular dynamics (MD) simulation techniques in order to explain functional mechanisms and most importantly to explore druggability against these proteins. Conformational analysis revealed novel insights into Vpr's conformational space, particularly the stable embedding of the Vpr C-terminal helix (residues 54-77) within lipid bilayers, marking its likely role as the transmembrane core of the ion channel structure. Full length Vpr undergoes large structural deviations inside lipid bilayer resulting in novel conformations of Vpr. The proposed multimeric Vpr ion channel models in this research offered the first rational attempt for structural understanding of this oligomeric complex which could enhance the therapeutic options. On the other hand, Viprinin and its two potent derivatives emerged as effective inhibitors for Vpr. These findings provide pivotal insights into structure-based drug discovery efforts against HIV-1 accessory proteins. The proposed ion channel models and inhibitor compounds establish a computational framework for future investigations into HIV-1 Vpr structural biology and drug development. Additionally, the analysis of Nef's conformational space identified a conserved druggable pocket implicated in homodimerization, presenting a potential therapeutic target. Utilizing fragment-based approaches, novel lead compounds against Nef were generated and further optimized through advanced MD simulations. These compounds could serve as the starting point for initial stage clinical trials for the discovery of new antiretroviral compounds targeting Nef. This research will lead to development of novel therapeutic options to combat HIV-1 infection in forseeable future in turn leading to significant decrease in loss of lives due to AIDS.