The DOI matches its Crossref record.
Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor
Open accessAbstract
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.
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Cited by
Kozal, M. J., Shah, N., Shen, N., Yang, R., Fucini, R., Merigan, T. C., Richman, D. D., Morris, D., Hubbell, E., Chee, M., et al. (1996) · Nature Medicine · doi:10.1038/nm0796-753 · Cited by 527
Replicative Fitness of Protease Inhibitor-Resistant Mutants of Human Immunodeficiency Virus Type 1
Martinez-Picado, J., Savara, A. V., Sutton, L., & D’Aquila, R. T. (1999) · Journal of Virology · doi:10.1128/jvi.73.5.3744-3752.1999 · Cited by 396
McDougall, B., King, P. J., Wu, B. W., Hostomsky, Z., Reinecke, M. G., & Robinson, W. E. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.1.140 · Cited by 210
Metadata
- Authors
- Ho, D. D., Toyoshima, T., Mo, H., Kempf, D. J., Norbeck, D., Chen, C. M., Wideburg, N. E., Burt, S. K., Erickson, J. W., & Singh, M. K.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 1994-03
- Volume
- 68
- Issue
- 3
- Pages
- 2016-2020
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W1537553846
- Cited by
- 212
- References
- 0
- FWCI
- 24.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ho, D. D., Toyoshima, T., Mo, H., Kempf, D. J., Norbeck, D., Chen, C. M., Wideburg, N. E., Burt, S. K., Erickson, J. W., & Singh, M. K. (1994). Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor. Journal of Virology. https://doi.org/10.1128/jvi.68.3.2016-2020.1994
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