Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
FORGE Life Science, Pennsylvania Biotechnology Center, Doylestown, PA 18901, USA.
Viruses. 2018 Nov 7;10(11):614. doi: 10.3390/v10110614.
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can cause serious complications in immunosuppressed and immunocompromised patients. Current anti-viral therapies target late stages of viral replication, and are often met with therapeutic resistance, necessitating the development of novel therapeutics. In this current study, we identified a naturally-occurring flavonoid compound, deguelin, which inhibits HCMV lytic replication. Our findings reveal that nanomolar concentrations of deguelin significantly suppress the production of the infectious virus. Further, we show that deguelin inhibits the lytic cycle during the phase of the replication cycle consistent with early (E) gene and protein expression. Importantly, our data reveal that deguelin inhibits replication of a ganciclovir-resistant strain of HCMV. Together, our findings identify a novel, naturally occurring compound that may prove useful in the treatment of HCMV replication.
人巨细胞病毒（HCMV）是一种普遍存在的疱疹病毒，目前尚无疫苗或治愈方法。这种病毒感染一旦获得，就是终身的，潜伏在造血细胞中。然而，免疫功能较弱的潜伏感染个体经常会发生 HCMV 重新激活，这可能导致免疫抑制和免疫功能低下的患者出现严重并发症。目前的抗病毒疗法针对病毒复制的晚期，并且经常遇到治疗耐药性，因此需要开发新的治疗方法。在本研究中，我们发现了一种天然存在的类黄酮化合物——藤黄菌素，它能抑制 HCMV 裂解复制。我们的研究结果表明，纳摩尔浓度的藤黄菌素能显著抑制感染性病毒的产生。此外，我们还发现藤黄菌素在复制周期的早期（E）基因和蛋白表达阶段抑制裂解周期。重要的是，我们的数据表明藤黄菌素抑制了更昔洛韦耐药株 HCMV 的复制。总之，我们的研究结果确定了一种新型的天然存在的化合物，它可能在治疗 HCMV 复制方面具有一定的应用价值。
