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Viruses 2010, 2(2), 606-638; doi:10.3390/v2020606
Review

Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase

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 and *
Christopher Bond Life Sciences Center & Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, Missouri 65211, USA
* Author to whom correspondence should be addressed.
Received: 2 December 2009 / Revised: 22 January 2010 / Accepted: 3 February 2010 / Published: 11 February 2010
(This article belongs to the Special Issue Retroviral Enzymes)
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Abstract

HIV-1 Reverse Transcriptase (HIV-1 RT) has been the target of numerous approved anti-AIDS drugs that are key components of Highly Active Anti-Retroviral Therapies (HAART). It remains the target of extensive structural studies that continue unabated for almost twenty years. The crystal structures of wild-type or drug-resistant mutant HIV RTs in the unliganded form or in complex with substrates and/or drugs have offered valuable glimpses into the enzyme’s folding and its interactions with DNA and dNTP substrates, as well as with nucleos(t)ide reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTIs) drugs. These studies have been used to interpret a large body of biochemical results and have paved the way for innovative biochemical experiments designed to elucidate the mechanisms of catalysis and drug inhibition of polymerase and RNase H functions of RT. In turn, the combined use of structural biology and biochemical approaches has led to the discovery of novel mechanisms of drug resistance and has contributed to the design of new drugs with improved potency and ability to suppress multi-drug resistant strains.
Keywords: HIV-1 reverse transcriptase; nucleoside RT inhibitors; non-nucleoside RT inhibitors; translocation defective RT inhibitors; drug resistance; excision HIV-1 reverse transcriptase; nucleoside RT inhibitors; non-nucleoside RT inhibitors; translocation defective RT inhibitors; drug resistance; excision
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Singh, K.; Marchand, B.; Kirby, K.A.; Michailidis, E.; Sarafianos, S.G. Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase. Viruses 2010, 2, 606-638.

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