HIV-1 Protease: Structural Perspectives on Drug Resistance

Antiviral inhibitors of HIV-1 protease are a notable success of structure-based drug design and have dramatically improved AIDS therapy. Analysis of the structures and activities of drug resistant protease variants has revealed novel molecular mechanisms of drug resistance and guided the design of t...

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Bibliographic Details
Published inViruses Vol. 1; no. 3; pp. 1110 - 1136
Main Authors Weber, Irene T, Agniswamy, Johnson
Format Journal Article Book Review
LanguageEnglish
Published Switzerland MDPI AG 01.12.2009
Molecular Diversity Preservation International (MDPI)
Subjects
aspartic protease
darunavir
drug resistance
molecular mechanism
protease inhibitors
Review
protease inhibitors
molecular mechanism
darunavir
drug resistance
aspartic protease
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Summary:Antiviral inhibitors of HIV-1 protease are a notable success of structure-based drug design and have dramatically improved AIDS therapy. Analysis of the structures and activities of drug resistant protease variants has revealed novel molecular mechanisms of drug resistance and guided the design of tight-binding inhibitors for resistant variants. The plethora of structures reveals distinct molecular mechanisms associated with resistance: mutations that alter the protease interactions with inhibitors or substrates; mutations that alter dimer stability; and distal mutations that transmit changes to the active site. These insights will inform the continuing design of novel antiviral inhibitors targeting resistant strains of HIV.
ISSN:1999-4915
1999-4915
DOI:10.3390/v1031110