Santos André L S, d'Avila-Levy Claudia M, Kneipp Lucimar F, Sodré Cátia L, Sangenito Leandro S, Branquinha Marta H
Laboratório de Investigação de Peptidases (LIP), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Bloco E-subsolo, Sala 05, Av. Carlos Chagas Filho 373, 21941-902, Rio de Janeiro. Brazil.
Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro. Brazil.
Curr Top Med Chem. 2017;17(11):1303-1317. doi: 10.2174/1568026616666161025161153.
The introduction of the HIV aspartic peptidase inhibitors (HIV-PIs) has revolutionized the medical arena, since they have drastically reduced the number and the severity of opportunistic infections, including the protozoal diseases that afflict the HIV-infected individuals worldwide. HIV-PIs rapidly and profoundly diminish the viral load, which is paralleled by increase in the CD4+ T lymphocyte counts and stimulation of the survival and activation of neutrophil, monocyte and endothelial cells, culminating in a vigorous reduction in the number of deaths due to the AIDS, in the number of new cases of AIDS and in the number of hospitalization days. Many research groups around the globe are trying to decipher both the in vitro and in vivo antiprotozoal mechanisms behind the use of HIVPIs. These studies have been supported by the urgent need to discover novel active compounds able to treat incurable parasitoses, including three major neglected diseases: malaria, leishmaniasis and Chagas' disease. The present review summarizes the recent advances on the effects of HIV-PIs against Plasmodium spp., Leishmania spp. and Trypanosoma cruzi.
HIV天冬氨酸蛋白酶抑制剂(HIV-PIs)的引入彻底改变了医学领域,因为它们极大地减少了机会性感染的数量和严重程度,包括困扰全球HIV感染者的原生动物疾病。HIV-PIs能迅速且显著地降低病毒载量,与此同时,CD4+T淋巴细胞计数增加,中性粒细胞、单核细胞和内皮细胞的存活及活化受到刺激,最终导致因艾滋病死亡的人数、新的艾滋病病例数以及住院天数大幅减少。全球许多研究团队都在试图解读使用HIV-PIs背后的体外和体内抗原生动物机制。这些研究得到了迫切需求的支持,即发现能够治疗无法治愈的寄生虫病的新型活性化合物,其中包括三种主要的被忽视疾病:疟疾、利什曼病和恰加斯病。本综述总结了HIV-PIs对疟原虫属、利什曼原虫属和克氏锥虫作用的最新进展。