Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
In silico study on HIV-PRIs substructures to terminate proteolytic activity in HTLV
Human T-lymphotropic virus (HTLV) is RNA retrovirus, which is causing CD3+ and CD4+ T-cell type leukemia and demyelinating diseases, like tropical spastic myelopathy. The replicative stage of the virus is one of the critical stages for the development of the disease. At present, there are no approved therapeutic agents targeting HTLV. HTLV mechanism of malignant cell growth in adult T-cell leukemia (ATL) /lymphoma, and the HTLV-PR has been an attractive target for anti cancer drug design. In comparison to other retroviruses HTLV also encodes protease (PR) enzyme, which is essential for maturation. Both HIV and HTLV proteases shows high structural similarity but known inhibitors of HIV-PR are not able to inhibit the HTLV-PR, while comparing the binding pocket of both proteases, MET37 of HTLV showing repulsive role with known HIV inhibitors. Functional analysis of M37A mutation clearly shows that MET37 is highly important for the protease function. Available inhibitors were tested against the HTLV-PR binding pocket and failed to interact with MET37. Screening of similar libraries of known compounds provides better interactions with MET37 and further validation with in vivo and in vitro studies on these screened compounds will provide more strength in discovering potent inhibitor for HTLV-PR.
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Poonam Singh 1*