Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China.
Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Re-emerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, China.
Sci Transl Med. 2020 Jun 3;12(546). doi: 10.1126/scitranslmed.aaz2254.
HIV-associated morbidity and mortality have markedly declined because of combinational antiretroviral therapy, but HIV readily mutates to develop drug resistance. Developing antivirals against previously undefined targets is essential to treat existing drug-resistant HIV strains. Some peptides derived from HIV-1 envelope glycoprotein (Env, gp120-gp41) have been shown to be effective in inhibiting HIV-1 infection. Therefore, we screened a peptide library from HIV-1 Env and identified a peptide from the cytoplasmic region, designated F9170, able to effectively inactivate HIV-1 virions and induce necrosis of HIV-1-infected cells, and reactivated latently infected cells. F9170 specifically targeted the conserved cytoplasmic tail of HIV-1 Env and effectively disrupted the integrity of the viral membrane. Short-term monoadministration of F9170 controlled viral loads to below the limit of detection in chronically SHIV-infected macaques. F9170 can enter the brain and lymph nodes, anatomic reservoirs for HIV latency. Therefore, F9170 shows promise as a drug candidate for HIV treatment.
由于联合抗逆转录病毒疗法，艾滋病毒相关发病率和死亡率显著下降，但艾滋病毒很容易发生突变以产生耐药性。开发针对以前未定义靶点的抗病毒药物对于治疗现有耐药性艾滋病毒株至关重要。一些源自 HIV-1 包膜糖蛋白（Env，gp120-gp41）的肽已被证明能有效抑制 HIV-1 感染。因此，我们从 HIV-1 Env 中筛选了一个肽文库，并鉴定出一个来自细胞质区域的肽，命名为 F9170，能够有效灭活 HIV-1 病毒颗粒并诱导 HIV-1 感染细胞坏死，并使潜伏感染的细胞重新激活。F9170 特异性靶向 HIV-1 Env 的保守细胞质尾巴，并有效地破坏了病毒膜的完整性。F9170 的短期单一给药可将慢性感染 SHIV 的猕猴体内的病毒载量控制在检测限以下。F9170 可以进入大脑和淋巴结，这是 HIV 潜伏的解剖储库。因此，F9170 有望成为治疗 HIV 的候选药物。
