Inhibiting the HIV integration process: past, present, and the future
- PMID: 24025027
- PMCID: PMC3926363
- DOI: 10.1021/jm400674a
Inhibiting the HIV integration process: past, present, and the future
Erratum in
- J Med Chem. 2014 Jul 24;57(14):6273
Abstract
HIV integrase (IN) catalyzes the insertion into the genome of the infected human cell of viral DNA produced by the retrotranscription process. The discovery of raltegravir validated the existence of the IN, which is a new target in the field of anti-HIV drug research. The mechanism of catalysis of IN is depicted, and the characteristics of the inhibitors of the catalytic site of this viral enzyme are reported. The role played by the resistance is elucidated, as well as the possibility of bypassing this problem. New approaches to block the integration process are depicted as future perspectives, such as development of allosteric IN inhibitors, dual inhibitors targeting both IN and other enzymes, inhibitors of enzymes that activate IN, activators of IN activity, as well as a gene therapy approach.
Figures














Similar articles
-
[How proviral DNA is integrated into the host cell DNA and how this process can be inhibited].Enferm Infecc Microbiol Clin. 2008 Nov;26 Suppl 12:11-6. doi: 10.1016/s0213-005x(08)76567-4. Enferm Infecc Microbiol Clin. 2008. PMID: 19572420 Review. Spanish.
-
HIV-1 integrase inhibitors: update and perspectives.Adv Pharmacol. 2008;56:199-228. doi: 10.1016/S1054-3589(07)56007-2. Adv Pharmacol. 2008. PMID: 18086413 Review. No abstract available.
-
HIV type 1 integrase inhibitors: from basic research to clinical implications.AIDS Rev. 2008 Jul-Sep;10(3):172-89. AIDS Rev. 2008. PMID: 18820719 Review.
-
Resistance to HIV-1 integrase inhibitors: A structural perspective.Drug Resist Updat. 2010 Aug-Oct;13(4-5):139-50. doi: 10.1016/j.drup.2010.05.001. Epub 2010 Jun 8. Drug Resist Updat. 2010. PMID: 20570551 Review.
-
Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization.Antimicrob Agents Chemother. 2012 Aug;56(8):4365-74. doi: 10.1128/AAC.00717-12. Epub 2012 Jun 4. Antimicrob Agents Chemother. 2012. PMID: 22664975 Free PMC article.
Cited by
-
Indole-based allosteric inhibitors of HIV-1 integrase.Bioorg Med Chem Lett. 2016 Oct 1;26(19):4748-4752. doi: 10.1016/j.bmcl.2016.08.037. Epub 2016 Aug 13. Bioorg Med Chem Lett. 2016. PMID: 27568085 Free PMC article.
-
Design, Synthesis, Docking Study, and Biological Evaluation of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide Derivatives as Anti-HIV-1 and Antibacterial Agents.Iran J Pharm Res. 2022 May 4;21(1):e126562. doi: 10.5812/ijpr-126562. eCollection 2022 Dec. Iran J Pharm Res. 2022. PMID: 36060913 Free PMC article.
-
Molecular dynamic simulations to investigate the structural impact of known drug resistance mutations on HIV-1C Integrase-Dolutegravir binding.PLoS One. 2020 May 7;15(5):e0223464. doi: 10.1371/journal.pone.0223464. eCollection 2020. PLoS One. 2020. PMID: 32379830 Free PMC article.
-
Progress in HIV-1 Integrase Inhibitors: A Review of their Chemical Structure Diversity.Iran J Pharm Res. 2016 Fall;15(4):595-628. Iran J Pharm Res. 2016. PMID: 28243261 Free PMC article. Review.
-
Elucidating the Molecular Determinants of the Binding Modes of a Third-Generation HIV-1 Integrase Strand Transfer Inhibitor: The Importance of Side Chain and Solvent Reorganization.Viruses. 2024 Jan 2;16(1):0. doi: 10.3390/v16010076. Viruses. 2024. PMID: 38257776 Free PMC article.
References
-
- Gottlieb M. S.; Schroff R.; Schanker H. M; Weisman J. D.; Fan P. T; Wolf R. A.; Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N. Engl. J. Med. 1981, 305, 1425–1431. - PubMed
-
- Masur H.; Michelis M. A.; Greene J. B.; Onorato I.; Stouwe R. A.; Holzman R. S.; Wormser G.; Brettman L.; Lange M.; Murray H. W.; Cunningham-Rundles S. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N. Engl. J. Med. 1981, 305, 1431–1438. - PubMed
-
- Siegal F. P.; Lopez C.; Hammer G. S.; Brown A. E.; Kornfeld S. J.; Gold J.; Hassett J.; Hirschman S. Z.; Cunningham-Rundles C.; Adelsberg B. R.; Parham D. M.; Siegal M.; Cunningham-Rundles S.; Armstrong D. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N. Engl. J. Med. 1981, 305, 1439–1444. - PubMed
-
- Cohen J. Therapies. Confronting the limits of success. Science 2002, 296, 2320–2324. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Chemical Information
Miscellaneous