Department of Microbiology & Immunology, Tulane University School of Medicine, New Orleans, LA, 70112, United States.
Neuroscience Program, Brain Institute, Tulane University, New Orleans, LA, 70112, United States.
Antiviral Res. 2021 Oct;194:105159. doi: 10.1016/j.antiviral.2021.105159. Epub 2021 Aug 11.
Human cytomegalovirus (HCMV) is a near ubiquitous herpesvirus that relies on host cell metabolism for efficient replication. Although it has been shown that HCMV requires functional host cell mitochondria for efficient replication, it is unknown whether mitochondrial targeted pharmacological agents can be repurposed as antivirals. Here we report that treatment with drugs targeting the electron transport chain (ETC) complexes inhibit HCMV replication. Addition of rotenone, oligomycin, antimycin and metformin resulted in decreased HCMV titers in vitro, independent of HCMV strain. This further illustrates the dependence of HCMV replication on functional mitochondria. Metformin, an FDA approved drug, delays HCMV replication kinetics resulting in a reduction of viral titers. Repurposing metformin as an antiviral is advantageous as its safety profile and epidemiological data are well accepted. Our findings provide new insight into the potential for targeting HCMV infection through host cell metabolism and how these pharmacological interventions function.
人类巨细胞病毒（HCMV）是一种近乎普遍存在的疱疹病毒，依赖宿主细胞代谢来实现高效复制。尽管已经表明 HCMV 需要功能正常的宿主细胞线粒体才能实现高效复制，但尚不清楚是否可以将靶向线粒体的药物重新用于抗病毒治疗。在这里，我们报告称，针对电子传递链（ETC）复合物的药物治疗可抑制 HCMV 复制。在体外，加入鱼藤酮、寡霉素、抗霉素和二甲双胍会降低 HCMV 的滴度，与 HCMV 株无关。这进一步说明了 HCMV 复制对功能正常的线粒体的依赖性。二甲双胍是一种获得 FDA 批准的药物，可延缓 HCMV 复制动力学，从而降低病毒滴度。将二甲双胍重新用于抗病毒治疗具有优势，因为其安全性和流行病学数据已被广泛接受。我们的研究结果为通过宿主细胞代谢靶向 HCMV 感染以及这些药物干预如何发挥作用提供了新的见解。
