rdf:type |
|
lifeskim:mentions |
umls-concept:C0013227,
umls-concept:C0021311,
umls-concept:C0026336,
umls-concept:C0031434,
umls-concept:C0033399,
umls-concept:C0035647,
umls-concept:C0235828,
umls-concept:C0598312,
umls-concept:C1175175,
umls-concept:C1175743,
umls-concept:C1292734,
umls-concept:C1522326,
umls-concept:C1522424
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pubmed:issue |
2
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pubmed:dateCreated |
2008-5-26
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pubmed:abstractText |
Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC(90)=8.3+/-2.8 microM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC(90)=6.1+/-4.3 microM). All compounds were toxic (IC(50)=6.6-74.5 microM) except for phenoxathiin (IC(50)=858+/-208 microM) and 10-(alpha-diethylamino-propionyl) phenothiazine.HCl (IC(50)=195+/-71.2 microM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1-3.3 microM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (-4h)/therapeutic regimen of 1, 10, or 50mg/(kg day) did not reduce virus lung titers at day 3, yet prolonged virus replication to 14 days. Similar therapeutic promazine doses were not efficacious. Thus, promazine did not affect SARS-CoV replication in vitro or in vivo, nor were any other phenothiazines efficacious in reducing virus replication. Therefore, treating SARS infections with compounds like promazine is not warranted.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-12711465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-12748632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-12883457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-12928031,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15016880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15105133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15110833,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15356152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15504263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15667124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15695582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-15878786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-16212898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-16339739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-16501078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-16597209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-16621037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-16830004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-2084068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-5294431,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18423639-9107383
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0166-3542
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
105-13
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18423639-Animals,
pubmed-meshheading:18423639-Antiviral Agents,
pubmed-meshheading:18423639-Cell Survival,
pubmed-meshheading:18423639-Cercopithecus aethiops,
pubmed-meshheading:18423639-Chemoprevention,
pubmed-meshheading:18423639-Cytokines,
pubmed-meshheading:18423639-Female,
pubmed-meshheading:18423639-Lung,
pubmed-meshheading:18423639-Mice,
pubmed-meshheading:18423639-Mice, Inbred BALB C,
pubmed-meshheading:18423639-Molecular Structure,
pubmed-meshheading:18423639-Neutral Red,
pubmed-meshheading:18423639-Phenothiazines,
pubmed-meshheading:18423639-SARS Virus,
pubmed-meshheading:18423639-Severe Acute Respiratory Syndrome,
pubmed-meshheading:18423639-Vero Cells,
pubmed-meshheading:18423639-Virus Replication
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pubmed:year |
2008
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pubmed:articleTitle |
Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections? Lack of efficacy of promazine on SARS-CoV replication in a mouse model.
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pubmed:affiliation |
Institute for Antiviral Research, Utah State University, 5600 Old Main Hill, Logan, UT 84322-5600, USA. dale.barnard@usu.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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