PREX-1979: Modeling the first ever prototype of a new generation of microbicides for preventing HIV infection among high risk women
Keywords:
HIV/AIDS, Novel Microbicides Strategies, Restriction Modification Systems, HIV genomes, Combination-Microbicides
Abstract
Impregnating a proteolytic substrate of specifity to viral envelope with a restriction enzyme cleaving the HIV genome could generate a novel line of microbicide. Web Cutter version 2.0 aimed at identifying which enzyme can cleave HIV-1 and 2 genomes in 10 or > cuts was employed. Computational analysis indicate that of 291, 17 (5.8%) enzymes had 10 or more cuts in the HIV- 1/SIVcpz genome as compared to 25 (8.9%) for HIV-2/SIVsmm with 6 enzymes (Eco-130I, EcoT141, ApoI, AcsI, BssTII, and StyI) having a mutual ability to cleave HIV-1 and 2 in 10 and more cuts. Although not a proteolytic enzyme, the surfactant Savvy/C31G (Cellegy) was identified as a safe and close candidate for our proteolytic substrate. With biochemical compound modeling, it is possible to stably impregnate the center of surfactant/detergent molecule with a natural product. The PREX Model may be explored to develop novel lines of microbicides aimed at preventing HIV and other viral STI transmission in humans
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