McMullan Laura K, Flint Mike, Dyall Julie, Albariño César, Olinger Gene G, Foster Scott, Sethna Phiroze, Hensley Lisa E, Nichol Stuart T, Lanier E Randall, Spiropoulou Christina F
Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Antiviral Res. 2016 Jan;125:71-8. doi: 10.1016/j.antiviral.2015.10.010. Epub 2015 Oct 23.
Brincidofovir (BCV) is the 3-hexadecyloxy-1-propanol (HDP) lipid conjugate of the acyclic nucleoside phosphonate cidofovir (CDV). BCV has established broad-spectrum activity against double-stranded DNA (dsDNA) viruses; however, its activity against RNA viruses has been less thoroughly evaluated. Here, we report that BCV inhibited infection of Ebola virus in multiple human cell lines. Unlike the mechanism of action for BCV against cytomegalovirus and other dsDNA viruses, phosphorylation of CDV to the diphosphate form appeared unnecessary. Instead, antiviral activity required the lipid moiety and in vitro activity against EBOV was observed for several HDP-nucleotide conjugates.
布林西多福韦（BCV）是无环核苷膦酸西多福韦（CDV）的3 - 十六烷氧基 - 1 - 丙醇（HDP）脂质共轭物。BCV已证实对双链DNA（dsDNA）病毒具有广谱活性；然而，其对RNA病毒的活性尚未得到充分评估。在此，我们报告BCV在多种人类细胞系中抑制埃博拉病毒感染。与BCV针对巨细胞病毒和其他dsDNA病毒的作用机制不同，CDV磷酸化为二磷酸形式似乎并非必需。相反，抗病毒活性需要脂质部分，并且几种HDP - 核苷酸共轭物在体外对埃博拉病毒具有活性。
