A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation - PubMed (original) (raw)
. 1990 Jan 26;247(4941):454-6.
doi: 10.1126/science.2405486.
Affiliations
- PMID: 2405486
- DOI: 10.1126/science.2405486
A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation
T J McQuade et al. Science. 1990.
Abstract
A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant Ki of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.
Similar articles
- Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues.
Meek TD, Lambert DM, Dreyer GB, Carr TJ, Tomaszek TA Jr, Moore ML, Strickler JE, Debouck C, Hyland LJ, Matthews TJ, et al. Meek TD, et al. Nature. 1990 Jan 4;343(6253):90-2. doi: 10.1038/343090a0. Nature. 1990. PMID: 1688646 - A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation.
[No authors listed] [No authors listed] Dis Markers. 1990 May-Jun;8(3):162-3. Dis Markers. 1990. PMID: 2125537 No abstract available. - Maturation of human immunodeficiency virus particles assembled from the gag precursor protein requires in situ processing by gag-pol protease.
Ross EK, Fuerst TR, Orenstein JM, O'Neill T, Martin MA, Venkatesan S. Ross EK, et al. AIDS Res Hum Retroviruses. 1991 May;7(5):475-83. doi: 10.1089/aid.1991.7.475. AIDS Res Hum Retroviruses. 1991. PMID: 1873082 - The gag proteins of human immunodeficiency virus type 1: mechanisms of virus assembly and possibilities for interference.
Modrow S, Kattenbeck B, von Poblotzki A, Niedrig M, Wagner R, Wolf H. Modrow S, et al. Med Microbiol Immunol. 1994 Sep;183(4):177-94. doi: 10.1007/BF00194171. Med Microbiol Immunol. 1994. PMID: 7845316 Review. No abstract available. - Cellular Targets of HIV-1 Protease: Just the Tip of the Iceberg?
Centazzo M, Manganaro L, Alvisi G. Centazzo M, et al. Viruses. 2023 Mar 9;15(3):712. doi: 10.3390/v15030712. Viruses. 2023. PMID: 36992421 Free PMC article. Review.
Cited by
- Quantitative Structure-Activity Relationship in the Series of 5-Ethyluridine, N2-Guanine, and 6-Oxopurine Derivatives with Pronounced Anti-Herpetic Activity.
Khairullina V, Martynova Y. Khairullina V, et al. Molecules. 2023 Nov 22;28(23):7715. doi: 10.3390/molecules28237715. Molecules. 2023. PMID: 38067446 Free PMC article. - 6D-QSAR for predicting biological activity of human aldose reductase inhibitors using quasar receptor surface modeling.
Sokouti B, Hamzeh-Mivehroud M. Sokouti B, et al. BMC Chem. 2023 Jun 22;17(1):63. doi: 10.1186/s13065-023-00970-x. BMC Chem. 2023. PMID: 37349775 Free PMC article. - Effectively predicting HIV-1 protease cleavage sites by using an ensemble learning approach.
Hu L, Li Z, Tang Z, Zhao C, Zhou X, Hu P. Hu L, et al. BMC Bioinformatics. 2022 Oct 27;23(1):447. doi: 10.1186/s12859-022-04999-y. BMC Bioinformatics. 2022. PMID: 36303135 Free PMC article. - Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques.
Okafor SN, Angsantikul P, Ahmed H. Okafor SN, et al. Int J Mol Sci. 2022 Oct 12;23(20):12149. doi: 10.3390/ijms232012149. Int J Mol Sci. 2022. PMID: 36293006 Free PMC article. - Structure-Activity-Relationship and Mechanistic Insights for Anti-HIV Natural Products.
Kaur R, Sharma P, Gupta GK, Ntie-Kang F, Kumar D. Kaur R, et al. Molecules. 2020 Apr 29;25(9):2070. doi: 10.3390/molecules25092070. Molecules. 2020. PMID: 32365518 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources