Overcoming HIV drug resistance through rational drug design based on molecular, biochemical, and structural profiles of HIV resistance.
There are 20 available drugs for the treatment of human immunodeficiency virus (HIV) infection. With a single exception, all of these drugs inhibit either HIV reverse transcriptase or protease. Reverse transcriptase inhibitors can be further categorized as nucleoside/nucleotide analogs or non-nucleoside reverse transcriptase inhibitors. Resistance that has emerged against all available antiretroviral drugs represents a major challenge in the therapy of HIV infection. Nevertheless, extensive analysis of the molecular and structural mechanisms by which such mutations confer resistance has accumulated over the years. This understanding has driven the development and refinement of novel compounds capable of maintaining antiviral activity against both wild-type and drug-resistant HIV strains. The molecular, biochemical, and structural profiles of reverse transcriptase inhibitor and protease inhibitor resistance are discussed. In addition, how this knowledge has been utilized to generate a new generation of antiviral drugs with activity against drug-resistant HIV is reviewed.
Yin
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Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, 10 Center Drive, Building 10, Room 5A11, Bethesda, ML 20892, USA.
Das
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D
Mitsuya
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D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D024882:Drug Resistance, Viral; D006678:HIV / Q000187:drug effects* / Q000201:enzymology; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009705:Nucleosides; D010455:Peptides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase