Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1066710.32607/20758251-2011-3-3-12-28ArticlesСтатьиReview ArticleClinical Use of Inhibitors of HIV-1 Integration: Problems and ProspectsClinical Use of Inhibitors of HIV-1 Integration: Problems and ProspectsKorolevS P

Department of Chemistry

spkorolev@mail.ruAgapkinaYu Yu

Department of Chemistry

GottikhM B

Department of Chemistry

Lomonosov Moscow State UniversityBelozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State University1509201133VOL 3, NO3 (2011)ТОМ 3, №3 (2011)122817012020Copyright ©; 2011, Korolev S.P., Agapkina Y.Y., Gottikh M.B.Copyright ©; 2011, Korolev S.P., Agapkina Y.Y., Gottikh M.B.2011Korolev S.P., Agapkina Y.Y., Gottikh M.B.Korolev S.P., Agapkina Y.Y., Gottikh M.B.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10667

The HIV-1 integrase enzyme is responsible for one of the key stages of retroviral replication; it acts as a catalyst for the integration of viral cDNA into the cell’s genome. Inhibitors of HIV-1 integration have been under development for over 10 years; yet, only one integration inhibitor, raltegravir, has been approved for clinical use so far. Raltegravir binds two metal ions in the enzyme’s active centre and blocks one of the integration stages: the strand transfer. Unfortunately, the clinical use of raltegravir results in the development of viral resistance among some patients. Several more HIV-1 integration inhibitors are undergoing clinical trials at the moment. However, the structure and mechanism of action of those are similar to raltegravir, which results in the emergence of cross resistance with raltegravir. The present review is focused on the history of the development and clinical trials of raltegravir and its analogues, the problems connected with the emergence of viral resistance to integration inhibitors, and the prospect of their future clinical use.

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