Identification of novel antipoxviral agents: Mitoxantrone inhibits vaccinia virus replication by blocking virion assembly Journal Article

   

Authors:	Deng, L.; Dai, P.; Ciro, A.; Smee, D. F.; Djaballah, H.; Shuman, S.
Article Title:	Identification of novel antipoxviral agents: Mitoxantrone inhibits vaccinia virus replication by blocking virion assembly
Abstract:	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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Keywords:	controlled study; unclassified drug; gene sequence; missense mutation; drug activity; nonhuman; antineoplastic agents; protein domain; animal cell; mouse; animals; mice; mus; gene expression; cell line; animal experiment; animal model; digoxin; drug screening; drug evaluation, preclinical; mice, inbred balb c; cell culture; nucleotide sequence; mitoxantrone; vaccinia virus; genome; antivirus agent; cidofovir; virus infection; virus replication; polydeoxyribonucleotide synthase; drug resistance, viral; virus protein; antiviral agents; virus assembly; vaccinia; variola virus; virus gene; virion; cycloheximide; cymarin; mycophenolic acid; microbial sensitivity tests; ancitabine; anisomycin; cephaeline; emetine; lanatoside c; lycorine; neriifolin; strophanthin; specific pathogen-free organisms
Journal Title:	Journal of Virology
Volume:	81
Issue:	24
ISSN:	0022-538X
Publisher:	American Society for Microbiology
Date Published:	2007-12-01
Start Page:	13392
End Page:	13402
Language:	English
DOI:	10.1128/jvi.00770-07
PUBMED:	17928345
PROVIDER:	scopus
PMCID:	PMC2168821
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-37048998961&partnerID=40&md5=2db8240b2bca794a1c3e669f09217a24
Notes:	--- - "Cited By (since 1996): 20" - "Export Date: 17 November 2011" - "CODEN: JOVIA" - "Molecular Sequence Numbers: GENBANK: NC_006998;" - "Source: Scopus"

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