DOI: 10.1128/jvi.68.3.2016-2020.1994. Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor

Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor

10.1128/jvi.68.3.2016-2020.1994

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

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.

Bibliography

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, 68(3), 2016â2020.

Authors 10

D D Ho (first)
T Toyoshima (additional)
H Mo (additional)
D J Kempf (additional)
D Norbeck (additional)
C M Chen (additional)
N E Wideburg (additional)
S K Burt (additional)
J W Erickson (additional)
M K Singh (additional)

References 0 Referenced 177

None

Dates

Type	When
Created	5 years, 7 months ago (Jan. 6, 2020, 11:46 a.m.)
Deposited	3 years, 5 months ago (March 4, 2022, 9:05 p.m.)
Indexed	3 months ago (May 18, 2025, 12:04 p.m.)
Issued	31 years, 5 months ago (March 1, 1994)
Published	31 years, 5 months ago (March 1, 1994)
Published Print	31 years, 5 months ago (March 1, 1994)

Funders 0

None

BibTeX

@article{Ho_1994, title={Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor}, volume={68}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.68.3.2016-2020.1994}, DOI={10.1128/jvi.68.3.2016-2020.1994}, number={3}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Ho, D D and Toyoshima, T and Mo, H and Kempf, D J and Norbeck, D and Chen, C M and Wideburg, N E and Burt, S K and Erickson, J W and Singh, M K}, year={1994}, month=mar, pages={2016–2020} }

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