The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus

Laura K. McMullan; Mike Flint; Julie Dyall; César Albariño; Gene G. Olinger; Scott Foster; Phiroze Sethna; Lisa E. Hensley; Stuart T. Nichol; E. Randall Lanier; Christina F. Spiropoulou

doi:10.1016/j.antiviral.2015.10.010

The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus

Laura K. McMullan, Mike Flint, Julie Dyall, César Albariño, Gene G. Olinger, Scott Foster, Phiroze Sethna, Lisa E. Hensley, Stuart T. Nichol, E. Randall Lanier, Christina F. Spiropoulou

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	71-78
Number of pages	8
Journal	Antiviral research
Volume	125
DOIs	https://doi.org/10.1016/j.antiviral.2015.10.010
State	Published - Jan 1 2016
Externally published	Yes

Keywords

Antiviral therapy
Brincidofovir
Ebola
In vitro screen

ASJC Scopus subject areas

Pharmacology
Virology

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10.1016/j.antiviral.2015.10.010

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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.",

keywords = "Antiviral therapy, Brincidofovir, Ebola, In vitro screen",

author = "McMullan, {Laura K.} and Mike Flint and Julie Dyall and C{\'e}sar Albari{\~n}o and Olinger, {Gene G.} and Scott Foster and Phiroze Sethna and Hensley, {Lisa E.} and Nichol, {Stuart T.} and Lanier, {E. Randall} and Spiropoulou, {Christina F.}",

note = "Publisher Copyright: {\textcopyright} 2015 Published by Elsevier B.V.",

year = "2016",

month = jan,

day = "1",

doi = "10.1016/j.antiviral.2015.10.010",

language = "English (US)",

volume = "125",

pages = "71--78",

journal = "Antiviral research",

issn = "0166-3542",

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AU - McMullan, Laura K.

AU - Flint, Mike

AU - Dyall, Julie

AU - Albariño, César

AU - Olinger, Gene G.

AU - Foster, Scott

AU - Sethna, Phiroze

AU - Hensley, Lisa E.

AU - Nichol, Stuart T.

AU - Lanier, E. Randall

AU - Spiropoulou, Christina F.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Antiviral therapy

KW - Brincidofovir

KW - Ebola

KW - In vitro screen

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DO - 10.1016/j.antiviral.2015.10.010

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SN - 0166-3542

VL - 125

SP - 71

EP - 78

JO - Antiviral research

JF - Antiviral research

ER -

The lipid moiety of brincidofovir is required for in vitro antiviral activity against Ebola virus

Abstract

Keywords

ASJC Scopus subject areas

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