Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly.

Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly. Research Abstract Details 

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Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly. Abstract Text:

Liang Deng,Peihong Dai,Anthony Ciro,Donald F Smee,Hakim Djaballah,Stewart Shuman,Liang Deng,Peihong Dai,Anthony Ciro,Donald F Smee,Hakim Djaballah,Stewart Shuman,

The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely target of the drug. Whole-genome sequencing of mitoxantrone-resistant viruses pinpointed missense mutations in the N-terminal domain of vaccinia DNA ligase. Despite its favorable activity in cell culture, mitoxantrone administered intraperitoneally at the maximum tolerated dose failed to protect mice against a lethal intranasal infection with vaccinia virus.

Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly. Publishing Authors By Initials

L Deng,P Dai,A Ciro,DF Smee,H Djaballah,S Shuman,L Deng,P Dai,A Ciro,DF Smee,H Djaballah,S Shuman,

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Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of virology

VOLUME: 81

Page Numbers: 13392-402

Journal Abbreviation: J. Virol.

ISSN: 1098-5514

DAY: 10

MONTH: 10

YEAR: 2007

Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly. Information

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LANGUAGE: eng

NlmUniqueID: 113724

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Grant and Affiliation Information for Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly.

AFFILIATION: Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Country: United States

AGENCY: United States NIAID

GRANT: U01 AI61456

ACRONYM: AI

MEDLINETA: J Virol

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