Comparative Study
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
Affiliations
- PMID: 8107264
- PMCID: PMC236669
- DOI: 10.1128/JVI.68.3.2016-2020.1994
Item in Clipboard
Comparative Study
Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor
J Virol.
1994 Mar.
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.
Similar articles
-
Selection of multiple human immunodeficiency virus type 1 variants that encode viral proteases with decreased sensitivity to an inhibitor of the viral protease.Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5597-601. doi: 10.1073/pnas.91.12.5597. Proc Natl Acad Sci U S A. 1994. PMID: 8202533 Free PMC article.
-
Design, synthesis, and resistance patterns of MP-134 and MP-167, two novel inhibitors of HIV type 1 protease.AIDS Res Hum Retroviruses. 1996 Jan 1;12(1):55-61. doi: 10.1089/aid.1996.12.55. AIDS Res Hum Retroviruses. 1996. PMID: 8825619
-
Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug.J Gen Virol. 1996 Mar;77 ( Pt 3):419-26. doi: 10.1099/0022-1317-77-3-419. J Gen Virol. 1996. PMID: 8601776
-
Structural mechanisms of HIV drug resistance.Annu Rev Pharmacol Toxicol. 1996;36:545-71. doi: 10.1146/annurev.pa.36.040196.002553. Annu Rev Pharmacol Toxicol. 1996. PMID: 8725401 Review.
-
Resilience to resistance of HIV-1 protease inhibitors: profile of darunavir.AIDS Rev. 2008 Jul-Sep;10(3):131-42. AIDS Rev. 2008. PMID: 18820715 Free PMC article. Review.
Cited by
-
Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: virus fitness in the absence and in the presence of drug.J Virol. 2000 Sep;74(18):8524-31. doi: 10.1128/jvi.74.18.8524-8531.2000. J Virol. 2000. PMID: 10954553 Free PMC article.
-
Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication.Antimicrob Agents Chemother. 2007 Feb;51(2):732-5. doi: 10.1128/AAC.00690-06. Epub 2006 Nov 13. Antimicrob Agents Chemother. 2007. PMID: 17101675 Free PMC article.
-
Evolution of human immunodeficiency virus type 1 protease genotypes and phenotypes in vivo under selective pressure of the protease inhibitor ritonavir.J Virol. 2005 Aug;79(16):10638-49. doi: 10.1128/JVI.79.16.10638-10649.2005. J Virol. 2005. PMID: 16051856 Free PMC article.
-
In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects.J Virol. 1996 Mar;70(3):2038-43. doi: 10.1128/JVI.70.3.2038-2043.1996. J Virol. 1996. PMID: 8627733 Free PMC article.
-
Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutations.Protein Sci. 2002 Oct;11(10):2393-402. doi: 10.1110/ps.0206702. Protein Sci. 2002. PMID: 12237461 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous
