GS-8374, a prototype phosphonate-containing inhibitor of HIV-1 protease, effectively inhibits protease mutants with amino acid insertions
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24371077
PubMed Central
PMC3957959
DOI
10.1128/jvi.02688-13
PII: JVI.02688-13
Knihovny.cz E-zdroje
- MeSH
- HIV infekce farmakoterapie virologie MeSH
- HIV-1 chemie účinky léků enzymologie genetika MeSH
- HIV-proteasa chemie genetika metabolismus MeSH
- inhibitory HIV-proteasy chemie farmakologie MeSH
- inzerční mutageneze * MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- molekulární modely MeSH
- organofosfonáty analýza MeSH
- sekvence aminokyselin MeSH
- vazebná místa MeSH
- virová léková rezistence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HIV-proteasa MeSH
- inhibitory HIV-proteasy MeSH
- organofosfonáty MeSH
- p16 protease, Human immunodeficiency virus 1 MeSH Prohlížeč
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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PDB
4M8X, 4M8Y