São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, 14800-903, Brazil; Institute of Chemistry, São Paulo State University (UNESP), Araraquara, Brazil.
São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, 14800-903, Brazil.
Eur J Med Chem. 2021 Mar 5;213:113213. doi: 10.1016/j.ejmech.2021.113213. Epub 2021 Jan 23.
Despite the advances in Human Immunodeficiency Virus (HIV) treatment, the cure for all HIV patients still poses a major challenge, which needs to be surpassed in the coming years. Among the strategies pursuing this aim, the 'kick-and-kill' approach, which involves the reactivation and elimination of a latent HIV reservoir that resides in some CD4 T cells, appears promising. The first step of this approach requires the use of latency reversal agents (LRAs) that induce the reactivation of the latent virus. Although several classes of LRAs have been reported so far, some limitations of these compounds still need to be overcome before their clinical use. The complete exhaustion of the reservoir of latent virus will contribute to promote the second step of this approach, facilitating the elimination of the reactivated HIV. Therefore, potent, safe, and non-toxic LRAs are necessary to promote efficient elimination of the HIV-1 virus from its reservoir. In this review article, we focus on the promising LRAs that have been described in the literature over the past few years, highlighting the advantages and disadvantages of their use in the 'kick and kill' approach, thus opening a new avenue in the development of a potential cure.
尽管人类免疫缺陷病毒 (HIV) 治疗取得了进展，但治愈所有 HIV 患者仍然是一个重大挑战，这需要在未来几年内得到解决。在追求这一目标的策略中，“踢杀”方法似乎很有前途，该方法涉及潜伏 HIV 储库的再激活和消除，该储库存在于一些 CD4 T 细胞中。该方法的第一步需要使用潜伏逆转剂 (LRA) 来诱导潜伏病毒的激活。尽管迄今为止已经报道了几类 LRA，但在这些化合物用于临床之前，仍需要克服其一些局限性。潜伏病毒库的完全耗尽将有助于促进该方法的第二步，促进被激活的 HIV 的消除。因此，需要有效的、安全的、无毒的 LRA 来促进 HIV-1 病毒从其储库中有效消除。在这篇综述文章中，我们重点介绍了过去几年文献中描述的有前途的 LRA，强调了它们在“踢杀”方法中的使用的优缺点，从而为潜在治愈方法的开发开辟了新途径。
