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.

尽管开发了有效的抗人类免疫缺陷病毒-1 (HIV-1) 疗法，但 HIV-1 相关病原体仍然是一个主要的临床问题。人类巨细胞病毒 (CMV) 是最常见的 HIV-1 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过早衰老相关的持续免疫激活的主要原因之一。在这里，我们报告了对 HIV-1 和 CMV 均具有活性的双靶向药物的开发。我们合成了七种化合物，它们构成抑制两种病原体的分子的结合物。我们发现所有七种化合物都表现出低细胞毒性，并有效抑制细胞系中的两种病毒。此外，体外共感染两种病毒。此类化合物的进一步开发可能会导致双靶向抗 CMV/HIV-1 药物的开发。