Download MendeleyGS-8374, a prototype phosphonate-containing inhibitor of HIV-1 protease, effectively inhibits protease mutants with amino acid insertions.
Grantz Saskova, K., Kozisek, M., Stray, K., de Jong, D., Rezaova, P., Brynda, J., van Maarseveen, N.M., Nijhuis, M., Cihlar, T., Konvalinka, J.(2014) J Virol 88: 3586-3590
- PubMed: 24371077
- DOI: https://doi.org/10.1128/JVI.02688-13
- Primary Citation of Related Structures:
4M8X, 4M8Y - PubMed Abstract:
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.
Organizational Affiliation:
Gilead Sciences and IOCB Research Center, Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Prague, Czech Republic.
