GS-8374, a prototype phosphonate-containing inhibitor of HIV-1 protease, effectively inhibits protease mutants with amino acid insertions

. 2014 Mar ; 88 (6) : 3586-90. [epub] 20131226

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid24371077

Insertions in the protease (PR) region of human immunodeficiency virus (HIV) represent an interesting mechanism of antiviral resistance against HIV PR inhibitors (PIs). Here, we demonstrate the improved ability of a phosphonate-containing experimental HIV PI, GS-8374, relative to that of other PIs, to effectively inhibit patient-derived recombinant HIV strains bearing PR insertions and numerous other mutations. We correlate enzyme inhibition with the catalytic activities of corresponding recombinant PRs in vitro and provide a biochemical and structural analysis of the PR-inhibitor complex.

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