Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor
| Autor: | M. K. Singh, T. Toyoshima, D. J. Kempf, David D. Ho, Chih-Ming Chen, S. K. Burt, N. E. Wideburg, Hongmei Mo, D. W. Norbeck, J. W. Erickson |
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| Rok vydání: | 1994 |
| Předmět: |
Models
Molecular Pyridines medicine.medical_treatment Molecular Sequence Data Immunology Antiviral Agents Microbiology Virus Structure-Activity Relationship HIV Protease Virology medicine HIV Protease Inhibitor Protease inhibitor (pharmacology) Amino Acid Sequence Selection Genetic chemistry.chemical_classification Methylurea Compounds Protease Base Sequence Dose-Response Relationship Drug Sequence Homology Amino Acid biology Genetic Variation Drug Resistance Microbial Valine HIV Protease Inhibitors In vitro NS2-3 protease Enzyme chemistry Enzyme inhibitor Drug Design Insect Science HIV-1 biology.protein Research Article |
| Zdroj: | Journal of Virology. 68:2016-2020 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.68.3.2016-2020.1994 |
| Popis: | Inhibitors of the human immunodeficiency virus type 1 protease represent a promising class of antiviral drugs for the treatment of AIDS, and several are now in clinical trials. Here, we report the in vitro selection of viral variants with decreased sensitivity to a C2-symmetric protease inhibitor (A-77003). We show that a single amino acid substitution (Arg to Gln or Lys) at position 8 of the protease results in a substantial decrease in the inhibitory activity of the drug on the enzyme and a comparable increase in viral resistance. These findings, when analyzed by using the three-dimensional structure of the protease-drug complex, provide a strategic guide for the future development of inhibitors of the human immunodeficiency virus type 1 protease. |
| Databáze: | OpenAIRE |
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