GS-8374, a Prototype Phosphonate-Containing Inhibitor of HIV-1 Protease, Effectively Inhibits Protease Mutants with Amino Acid Insertions
| Autor: | Jan Konvalinka, Tomáš Cihlář, Dorien de Jong, Kirsten M. Stray, Jiří Brynda, Noortje M van Maarseveen, Milan Kožíšek, Pavlína Řezáčová, Monique Nijhuis, Klára Grantz Šašková |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular medicine.medical_treatment Immunology Mutant Organophosphonates HIV Infections Biology Crystallography X-Ray Microbiology law.invention HIV Protease HIV-1 protease law Virology Drug Resistance Viral Vaccines and Antiviral Agents medicine Humans HIV Protease Inhibitor Amino Acid Sequence Binding site Peptide sequence chemistry.chemical_classification Binding Sites Protease virus diseases HIV Protease Inhibitors Molecular biology Amino acid Mutagenesis Insertional chemistry Insect Science HIV-1 biology.protein Recombinant DNA |
| Zdroj: | Journal of Virology. 88:3586-3590 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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