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THE PHARMA REVIEW (JAN 2010)

Emerging Drug Targets for HIV Therapy: A Review

Swapnil Nawale, Shashank Neve, V.J. Kadam, M.P. Toraskar

Abstract: The viral enzymes reverse transcriptase and protease are the current targets for antiretroviral therapy (ART). The use of a combination of inhibitors targeting these enzymes can reduce viral load for a prolonged period and delay disease progression. However, complications of ART, including the emergence of viruses resistant to current drugs, are driving the development of new antiretroviral agents targeting not only the reverse transcriptase and protease enzymes but novel targets as well. CCR5 and Integrase inhibitors have recently been approved for use in HIV treatment. The durg targets, which are under investigation, include CCR5 and CXCR4, maturation inhibitors, gene therapy, viral envelope protein (env). Novel virus that targets HIV-1-infected cells and Human deoxyhypusine synthase (DHS) are discussed as novel targets for HIV therapy.A multifaceted approach to ART, using combinations of inhibitors that target different steps of the viral life cycle, has the best potential for long-term control of HIV infection. This review outlines the key drug targets and steps where pharmacologic intervention can have a favorable therapeutic benefit.

Introduction: Current targets for antiretroviral therapy (ART) include the viral enzymes reverse transcriptase and protease. The use of a combination of inhibitors reduce viral load for a prolonged period and delay disease progression. The existence of viruses resistant to current antiretroviral, and transmission of drug-resistant strains, complication and toxicity of current regimen are driving the development of new antiretroviral agents targeting not only the reverse transcriptase and protease enzymes but novel targets as well.
HIV entry into susceptible cells, the integration of HIV DNA into the host cell genome, virion maturation etc. are currently promising emerging targets for ART as shown in figure 1. Inhibitors of novel targets are most likely to be fully active against resistant viruses and present new treatment options for individuals with multi drug resistant viruses. Therefore, inhibitors against new targets will complement and diversify current treatment options, and may act additively or synergistically with other inhibitors.

 

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