Department of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Department of Microbiology & Immunology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Bioorg Med Chem. 2019 May 1;27(9):1795-1803. doi: 10.1016/j.bmc.2019.03.026. Epub 2019 Mar 13.
Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses.
机会性病毒是免疫抑制个体的主要问题，尤其是在器官或干细胞移植后。目前的治疗方法要么不存在，要么存在毒性高或产生耐药株等问题。我们之前发表过，一种针对宿主蛋白的运输抑制剂可大大减少人巨细胞病毒的复制。该抑制剂对多瘤病毒（另一种机会性病毒家族）也显示出一定的疗效。我们为此抑制剂开发了一系列类似物，并表明这些类似物保持了对 HCMV 的高效性，同时大大降低了抑制多瘤病毒复制所需的浓度。通过靶向宿主蛋白，这些化合物能够抑制两种非常不同的病毒的复制。这些观察结果为免疫抑制个体开辟了可能，为他们提供了针对多种不同机会性病毒的有效泛病毒抑制剂。
