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Generation of a long-acting fusion inhibitor against HIV-1.

ABSTRACT: AIDS has evolved from a fatal infectious disease to a manageable chronic disease under the treatment of anti-AIDS medications. HIV fusion inhibitors with high activity, low side effects and strong selectivity are promising drugs against HIV. Only one fusion inhibitor is currently approved, thereby highly active long-acting fusion inhibitors need to be developed for long-term AIDS treatment. Here, we synthesised MT-SC22EK (a small HIV fusion inhibitor) derivatives containing 1-2 staples to improve its stability. Antiviral activity studies showed that MT-SC22EK-2 with two staples exhibited potent inhibitory activity against HIV-1 standard strains and Chinese epidemic strains, and at the same time, MT-SC22EK-2 presented strong anti-T20 resistance. Surprisingly, MT-SC22EK-2 possessed excellent protease stability with a half-life of 3665 min. MT-SC22EK-2 is a potential HIV fusion inhibitor considered as a long-acting anti-HIV drug candidate.

SUBMITTER: Guo Y

PROVIDER: S-EPMC6071707 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Generation of a long-acting fusion inhibitor against HIV-1.

Guo Ye Y Zhou Pan-Pan PP Zhang Sen-Yan SY Fan Xiao-Wen XW Dou Yu-Wei YW Shi Xuan-Ling XL

MedChemComm 20180606 7

AIDS has evolved from a fatal infectious disease to a manageable chronic disease under the treatment of anti-AIDS medications. HIV fusion inhibitors with high activity, low side effects and strong selectivity are promising drugs against HIV. Only one fusion inhibitor is currently approved, thereby highly active long-acting fusion inhibitors need to be developed for long-term AIDS treatment. Here, we synthesised MT-SC22EK (a small HIV fusion inhibitor) derivatives containing 1-2 staples to improv ...[more]

PMID: 30109011

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