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HIV-1 Protease: Structural Perspectives on Drug Resistance.

ABSTRACT: 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.

SUBMITTER: Weber IT

PROVIDER: S-EPMC3185505 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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HIV-1 Protease: Structural Perspectives on Drug Resistance.

Weber Irene T IT Agniswamy Johnson J

Viruses 20091203 3

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 inhibit ...[more]

PMID: 21994585

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