Abstract:
:We have analyzed a panel of protein kinase inhibitors (PKIs) and found that some indolocarbazoles (Gö6976, K252a, K252c) proved to be highly effective inhibitors of GCV-sensitive and -resistant human cytomegalovirus (HCMV) strains, but did not show any effect against herpes simplex virus. Antiviral activity was determined by focus reduction assays (IC(50) ranging from 0.009 to 0.4 microM). Other inhibitors of serine/threonine kinases (Gö6850, H-7, roscovitine) were found to be ineffective. Virus yield at 5 days after infection was reduced by three orders of magnitude with nanomolar concentrations of the indolocarbazoles. These compounds were fully effective when added up to 24 h post infection and showed reduced activity up to 72 h post infection. Cytotoxicity assays in proliferating and non-proliferating cells demonstrated that the effective antiviral concentration of these compounds was significantly lower than either antiproliferative (IC(50)/CC(50) ranging from 6.5 to 390) or cytotoxic (IC(50)/CC(50) ranging from 72. 5 to 1000) doses. The effects of PKIs on the virus-encoded protein kinase pUL97 were studied using recombinant vaccinia viruses. Indolocarbazoles strongly inhibited both pUL97 autophosphorylation (IC(50) ranging from 0.0012 to 0.013 microM) and pUL97-dependent ganciclovir phosphorylation (IC(50) ranging from 0.05 to 0.26 microM). Other inhibitors of serine/threonine kinases showed only weak (Gö6850) or no (H-7, roscovitine) effect on these pUL97 functions, while oxoflavone tyrosine kinase inhibitors had no effect at all.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Zimmermann A,Wilts H,Lenhardt M,Hahn M,Mertens Tdoi
10.1016/s0166-3542(00)00118-2subject
Has Abstractpub_date
2000-10-01 00:00:00pages
49-60issue
1eissn
0166-3542issn
1872-9096pii
S0166-3542(00)00118-2journal_volume
48pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1996-12-01 00:00:00
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journal_title:Antiviral research
pub_type: 杂志文章
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journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2004.09.005
更新日期:2005-01-01 00:00:00
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journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2015.09.002
更新日期:2015-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.antiviral.2011.01.001
更新日期:2011-03-01 00:00:00
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journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2005.06.003
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Antiviral research
pub_type: 杂志文章
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journal_title:Antiviral research
pub_type: 杂志文章,评审
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更新日期:2006-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1986-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0166-3542(84)90033-0
更新日期:1984-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.antiviral.2019.104554
更新日期:2019-09-01 00:00:00
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journal_title:Antiviral research
pub_type: 杂志文章,meta分析
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更新日期:2011-02-01 00:00:00
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journal_title:Antiviral research
pub_type: 杂志文章,评审
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journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2011.06.013
更新日期:2011-10-01 00:00:00