Engelhardt Institute of Molecular Biology, Vavilova Str., 32, Moscow, 119991, Russia.
Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Biochimie. 2021 Oct;189:169-180. doi: 10.1016/j.biochi.2021.06.011. Epub 2021 Jun 29.
Despite the development of efficient anti-human immunodeficiency virus-1 (HIV-1) therapy, HIV-1 associated pathogens remain a major clinical problem. Human cytomegalovirus (CMV) is among the most common HIV-1 copathogens and one of the main causes of persistent immune activation associated with dysregulation of the immune system, cerebrovascular and cardiovascular pathologies, and premature aging. Here, we report on the development of dual-targeted drugs with activity against both HIV-1 and CMV. We synthesized seven compounds that constitute conjugates of molecules that suppress both pathogens. We showed that all seven compounds exhibit low cytotoxicity and efficiently inhibited both viruses in cell lines. Furthermore, we chose a representative compound and demonstrated that it efficiently suppressed replication of HIV-1 and CMV in human lymphoid tissue ex vivo coinfected with both viruses. Further development of such compounds may lead to the development of dual-targeted anti-CMV/HIV-1 drugs.
尽管抗人类免疫缺陷病毒-1（HIV-1）的疗法已经取得了进展，但 HIV-1 相关病原体仍然是一个主要的临床问题。人巨细胞病毒（CMV）是 HIV-1 最常见的共病原体之一，也是与免疫系统失调、脑血管和心血管疾病以及早衰相关的持续免疫激活的主要原因之一。在这里，我们报告了针对 HIV-1 和 CMV 的双重靶向药物的开发。我们合成了七种化合物，这些化合物是抑制这两种病原体的分子的缀合物。我们表明，这七种化合物均表现出低细胞毒性，并能有效地抑制细胞系中的两种病毒。此外，我们选择了一种代表性化合物，并证明它能有效地抑制两种病毒共感染的人淋巴组织外感染中 HIV-1 和 CMV 的复制。进一步开发此类化合物可能会导致开发针对 CMV/HIV-1 的双重靶向药物。
