title: The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus.
abstract: 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.
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: McMullan
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Flint
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Dyall
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: César
authors.initials: C
authors.lastname: Albariño
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.affiliation: Chimerix, Durham, NC, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Foster
authors.affiliation: Chimerix, Durham, NC, USA.
authors.forename: Phiroze
authors.initials: P
authors.lastname: Sethna
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Chimerix, Durham, NC, USA.
authors.forename: E Randall
authors.initials: ER
authors.lastname: Lanier
authors.affiliation: Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: ccs8@cdc.gov.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D029043:Ebolavirus / Q000187:drug effects*; D006367:HeLa Cells; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D008055:Lipids; D063065:Organophosphonates; C525733:brincidofovir; D003596:Cytosine; D000077404:Cidofovir
keywords: Antiviral therapy; Brincidofovir; Ebola; In vitro screen