SrasV1, PascalFrancis, Curation, bibRecord, 000712

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

Identifieur interne : 000712 ( PascalFrancis/Curation ); précédent : 000711; suivant : 000713

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

Auteurs : Dale L. Barnard [États-Unis] ; Craig W. Day [États-Unis] ; Kevin Bailey [États-Unis] ; Matthew Heiner [États-Unis] ; Robert Montgomery [États-Unis] ; Larry Lauridsen [États-Unis] ; Kie-Hoon Jung [États-Unis] ; Joseph K.-K. Li [États-Unis] ; Paul K. S. Chan [Hong Kong] ; Robert W. Sidwell [États-Unis]

Source :

Antiviral research [ 0166-3542 ] ; 2008.

RBID : Pascal:08-0298379

Descripteurs français

Pascal (Inist)
- Antipsychotique, Neuroleptique, Relation structure activité, Promazine, Antiviral, Syndrome respiratoire aigu sévère, Virus syndrome respiratoire aigu sévère, Réplication, Modèle animal, Souris, Psychotrope.

English descriptors

KwdEn :
- Animal model, Antipsychotic, Antiviral, Mouse, Neuroleptic, Promazine, Psychotropic, Replication, Severe acute respiratory syndrome, Severe acute respiratory syndrome virus, Structure activity relation.

Abstract

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 EC₉₀ = 8.3 ± 2.8 μM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC₉₀ = 6.1 ± 4.3 μM). All compounds were toxic (IC₅₀ = 6.6-74.5 μM) except for phenoxathiin (IC₅₀ = 858 ± 208 μM) and 10-(alpha-diethylamino-propionyl) phenothiazine.HCl (IC₅₀ =195 ± 71.2 μM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1-3.3 μM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (-4 h)/therapeutic regimen of 1, 10, or 50 mg/(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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A08	`01`	`1`	`ENG`	`@1 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`
A11	`01`	`1`		`@1 BARNARD (Dale L.)`
A11	`02`	`1`		`@1 DAY (Craig W.)`
A11	`03`	`1`		`@1 BAILEY (Kevin)`
A11	`04`	`1`		`@1 HEINER (Matthew)`
A11	`05`	`1`		`@1 MONTGOMERY (Robert)`
A11	`06`	`1`		`@1 LAURIDSEN (Larry)`
A11	`07`	`1`		`@1 JUNG (Kie-Hoon)`
A11	`08`	`1`		`@1 LI (Joseph K.-K.)`
A11	`09`	`1`		`@1 CHAN (Paul K. S.)`
A11	`10`	`1`		`@1 SIDWELL (Robert W.)`
A14	`01`			`@1 Institute for Antiviral Research, Utah State University, 5600 Old Main Hill @2 Logan, UT 84322-5600 @3 USA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 5 aut. @Z 6 aut. @Z 7 aut. @Z 10 aut.`
A14	`02`			`@1 Department of Biology, Utah State University, 5305 Old Main Hill @2 Logan, UT 84322-5305 @3 USA @Z 8 aut.`
A14	`03`			`@1 Department of Microbiology, Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, 1/F Prince of Wales Hospital @2 Shatin, New Territories @3 HKG @Z 9 aut.`
A20				`@1 105-113`
A21				`@1 2008`
A23	`01`			`@0 ENG`
A43	`01`			`@1 INIST @2 18839 @5 354000200257640040`
A44				`@0 0000 @1 © 2008 INIST-CNRS. All rights reserved.`
A45				`@0 3/4 p.`
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A66	`01`			`@0 NLD`
C01	`01`		`ENG`	@0 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 EC₉₀ = 8.3 ± 2.8 μM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC₉₀ = 6.1 ± 4.3 μM). All compounds were toxic (IC₅₀ = 6.6-74.5 μM) except for phenoxathiin (IC₅₀ = 858 ± 208 μM) and 10-(alpha-diethylamino-propionyl) phenothiazine.HCl (IC₅₀ =195 ± 71.2 μM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1-3.3 μM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (-4 h)/therapeutic regimen of 1, 10, or 50 mg/(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.
C02	`01`	`X`		`@0 002B02S05`
C02	`02`	`X`		`@0 002B05C02C`
C03	`01`	`X`	`FRE`	`@0 Antipsychotique @5 01`
C03	`01`	`X`	`ENG`	`@0 Antipsychotic @5 01`
C03	`01`	`X`	`SPA`	`@0 Antipsicótico @5 01`
C03	`02`	`X`	`FRE`	`@0 Neuroleptique @5 02`
C03	`02`	`X`	`ENG`	`@0 Neuroleptic @5 02`
C03	`02`	`X`	`SPA`	`@0 Neuroléptico @5 02`
C03	`03`	`X`	`FRE`	`@0 Relation structure activité @5 03`
C03	`03`	`X`	`ENG`	`@0 Structure activity relation @5 03`
C03	`03`	`X`	`SPA`	`@0 Relación estructura actividad @5 03`
C03	`04`	`X`	`FRE`	`@0 Promazine @2 NK @2 FR @5 04`
C03	`04`	`X`	`ENG`	`@0 Promazine @2 NK @2 FR @5 04`
C03	`04`	`X`	`SPA`	`@0 Promazina @2 NK @2 FR @5 04`
C03	`05`	`X`	`FRE`	`@0 Antiviral @5 05`
C03	`05`	`X`	`ENG`	`@0 Antiviral @5 05`
C03	`05`	`X`	`SPA`	`@0 Antiviral @5 05`
C03	`06`	`X`	`FRE`	`@0 Syndrome respiratoire aigu sévère @2 NM @5 07`
C03	`06`	`X`	`ENG`	`@0 Severe acute respiratory syndrome @2 NM @5 07`
C03	`06`	`X`	`SPA`	`@0 Síndrome respiratorio agudo severo @2 NM @5 07`
C03	`07`	`X`	`FRE`	`@0 Virus syndrome respiratoire aigu sévère @2 NW @5 10`
C03	`07`	`X`	`ENG`	`@0 Severe acute respiratory syndrome virus @2 NW @5 10`
C03	`07`	`X`	`SPA`	`@0 Severe acute respiratory syndrome virus @2 NW @5 10`
C03	`08`	`X`	`FRE`	`@0 Réplication @5 11`
C03	`08`	`X`	`ENG`	`@0 Replication @5 11`
C03	`08`	`X`	`SPA`	`@0 Replicación @5 11`
C03	`09`	`X`	`FRE`	`@0 Modèle animal @5 12`
C03	`09`	`X`	`ENG`	`@0 Animal model @5 12`
C03	`09`	`X`	`SPA`	`@0 Modelo animal @5 12`
C03	`10`	`X`	`FRE`	`@0 Souris @5 14`
C03	`10`	`X`	`ENG`	`@0 Mouse @5 14`
C03	`10`	`X`	`SPA`	`@0 Ratón @5 14`
C03	`11`	`X`	`FRE`	`@0 Psychotrope @2 FX @5 26`
C03	`11`	`X`	`ENG`	`@0 Psychotropic @2 FX @5 26`
C03	`11`	`X`	`SPA`	`@0 Psicotropo @2 FX @5 26`
C07	`01`	`X`	`FRE`	`@0 Virose`
C07	`01`	`X`	`ENG`	`@0 Viral disease`
C07	`01`	`X`	`SPA`	`@0 Virosis`
C07	`02`	`X`	`FRE`	`@0 Infection`
C07	`02`	`X`	`ENG`	`@0 Infection`
C07	`02`	`X`	`SPA`	`@0 Infección`
C07	`03`	`X`	`FRE`	`@0 Coronavirus @2 NW`
C07	`03`	`X`	`ENG`	`@0 Coronavirus @2 NW`
C07	`03`	`X`	`SPA`	`@0 Coronavirus @2 NW`
C07	`04`	`X`	`FRE`	`@0 Coronaviridae @2 NW`
C07	`04`	`X`	`ENG`	`@0 Coronaviridae @2 NW`
C07	`04`	`X`	`SPA`	`@0 Coronaviridae @2 NW`
C07	`05`	`X`	`FRE`	`@0 Nidovirales @2 NW`
C07	`05`	`X`	`ENG`	`@0 Nidovirales @2 NW`
C07	`05`	`X`	`SPA`	`@0 Nidovirales @2 NW`
C07	`06`	`X`	`FRE`	`@0 Virus @2 NW`
C07	`06`	`X`	`ENG`	`@0 Virus @2 NW`
C07	`06`	`X`	`SPA`	`@0 Virus @2 NW`
C07	`07`	`X`	`FRE`	`@0 Rodentia @2 NS`
C07	`07`	`X`	`ENG`	`@0 Rodentia @2 NS`
C07	`07`	`X`	`SPA`	`@0 Rodentia @2 NS`
C07	`08`	`X`	`FRE`	`@0 Mammalia @2 NS`
C07	`08`	`X`	`ENG`	`@0 Mammalia @2 NS`
C07	`08`	`X`	`SPA`	`@0 Mammalia @2 NS`
C07	`09`	`X`	`FRE`	`@0 Vertebrata @2 NS`
C07	`09`	`X`	`ENG`	`@0 Vertebrata @2 NS`
C07	`09`	`X`	`SPA`	`@0 Vertebrata @2 NS`
C07	`10`	`X`	`FRE`	`@0 Dérivé de la phénothiazine @5 37`
C07	`10`	`X`	`ENG`	`@0 Phenothiazine derivatives @5 37`
C07	`10`	`X`	`SPA`	`@0 Fenotiazina derivado @5 37`
C07	`11`	`X`	`FRE`	`@0 Pathologie de l'appareil respiratoire @5 38`
C07	`11`	`X`	`ENG`	`@0 Respiratory disease @5 38`
C07	`11`	`X`	`SPA`	`@0 Aparato respiratorio patología @5 38`
C07	`12`	`X`	`FRE`	`@0 Pathologie des poumons @5 39`
C07	`12`	`X`	`ENG`	`@0 Lung disease @5 39`
C07	`12`	`X`	`SPA`	`@0 Pulmón patología @5 39`
N21				`@1 189`

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Pascal:08-0298379

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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</title>
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<author><name sortKey="Heiner, Matthew" sort="Heiner, Matthew" uniqKey="Heiner M" first="Matthew" last="Heiner">Matthew Heiner</name>
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<author><name sortKey="Montgomery, Robert" sort="Montgomery, Robert" uniqKey="Montgomery R" first="Robert" last="Montgomery">Robert Montgomery</name>
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</author>
<author><name sortKey="Lauridsen, Larry" sort="Lauridsen, Larry" uniqKey="Lauridsen L" first="Larry" last="Lauridsen">Larry Lauridsen</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute for Antiviral Research, Utah State University, 5600 Old Main Hill</s1>
<s2>Logan, UT 84322-5600</s2>
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<country>États-Unis</country>
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</author>
<author><name sortKey="Jung, Kie Hoon" sort="Jung, Kie Hoon" uniqKey="Jung K" first="Kie-Hoon" last="Jung">Kie-Hoon Jung</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute for Antiviral Research, Utah State University, 5600 Old Main Hill</s1>
<s2>Logan, UT 84322-5600</s2>
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<author><name sortKey="Li, Joseph K K" sort="Li, Joseph K K" uniqKey="Li J" first="Joseph K.-K." last="Li">Joseph K.-K. Li</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Biology, Utah State University, 5305 Old Main Hill</s1>
<s2>Logan, UT 84322-5305</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
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<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Chan, Paul K S" sort="Chan, Paul K S" uniqKey="Chan P" first="Paul K. S." last="Chan">Paul K. S. Chan</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Microbiology, Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, 1/F Prince of Wales Hospital</s1>
<s2>Shatin, New Territories</s2>
<s3>HKG</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
</affiliation>
</author>
<author><name sortKey="Sidwell, Robert W" sort="Sidwell, Robert W" uniqKey="Sidwell R" first="Robert W." last="Sidwell">Robert W. Sidwell</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute for Antiviral Research, Utah State University, 5600 Old Main Hill</s1>
<s2>Logan, UT 84322-5600</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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</analytic>
<series><title level="j" type="main">Antiviral research</title>
<title level="j" type="abbreviated">Antivir. res.</title>
<idno type="ISSN">0166-3542</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
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<seriesStmt><title level="j" type="main">Antiviral research</title>
<title level="j" type="abbreviated">Antivir. res.</title>
<idno type="ISSN">0166-3542</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal model</term>
<term>Antipsychotic</term>
<term>Antiviral</term>
<term>Mouse</term>
<term>Neuroleptic</term>
<term>Promazine</term>
<term>Psychotropic</term>
<term>Replication</term>
<term>Severe acute respiratory syndrome</term>
<term>Severe acute respiratory syndrome virus</term>
<term>Structure activity relation</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Antipsychotique</term>
<term>Neuroleptique</term>
<term>Relation structure activité</term>
<term>Promazine</term>
<term>Antiviral</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Réplication</term>
<term>Modèle animal</term>
<term>Souris</term>
<term>Psychotrope</term>
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</textClass>
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<front><div type="abstract" xml:lang="en">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<sub>90</sub>
 = 8.3 ± 2.8 μM, 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<sub>90</sub>
 = 6.1 ± 4.3 μM). All compounds were toxic (IC<sub>50</sub>
 = 6.6-74.5 μM) except for phenoxathiin (IC<sub>50</sub>
 = 858 ± 208 μM) and 10-(alpha-diethylamino-propionyl) phenothiazine.HCl (IC<sub>50</sub>
 =195 ± 71.2 μM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1-3.3 μM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (-4 h)/therapeutic regimen of 1, 10, or 50 mg/(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.</div>
</front>
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<fA08 i1="01" i2="1" l="ENG"><s1>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</s1>
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<fA11 i1="09" i2="1"><s1>CHAN (Paul K. S.)</s1>
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<fA11 i1="10" i2="1"><s1>SIDWELL (Robert W.)</s1>
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<s2>Shatin, New Territories</s2>
<s3>HKG</s3>
<sZ>9 aut.</sZ>
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<fC01 i1="01" l="ENG"><s0>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<sub>90</sub>
 = 8.3 ± 2.8 μM, 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<sub>90</sub>
 = 6.1 ± 4.3 μM). All compounds were toxic (IC<sub>50</sub>
 = 6.6-74.5 μM) except for phenoxathiin (IC<sub>50</sub>
 = 858 ± 208 μM) and 10-(alpha-diethylamino-propionyl) phenothiazine.HCl (IC<sub>50</sub>
 =195 ± 71.2 μM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1-3.3 μM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (-4 h)/therapeutic regimen of 1, 10, or 50 mg/(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.</s0>
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<s5>01</s5>
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<fC03 i1="01" i2="X" l="ENG"><s0>Antipsychotic</s0>
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<fC03 i1="04" i2="X" l="FRE"><s0>Promazine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Promazine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Promazina</s0>
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<s2>FR</s2>
<s5>04</s5>
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<fC03 i1="05" i2="X" l="FRE"><s0>Antiviral</s0>
<s5>05</s5>
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<fC03 i1="05" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0>
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<fC03 i1="06" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0>
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<s5>07</s5>
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<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0>
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<s5>10</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0>
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<s5>10</s5>
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<fC03 i1="07" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>10</s5>
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<fC03 i1="08" i2="X" l="FRE"><s0>Réplication</s0>
<s5>11</s5>
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</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Replicación</s0>
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<fC03 i1="09" i2="X" l="ENG"><s0>Animal model</s0>
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<fC03 i1="10" i2="X" l="FRE"><s0>Souris</s0>
<s5>14</s5>
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<fC03 i1="10" i2="X" l="ENG"><s0>Mouse</s0>
<s5>14</s5>
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<fC03 i1="10" i2="X" l="SPA"><s0>Ratón</s0>
<s5>14</s5>
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<s2>FX</s2>
<s5>26</s5>
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<s2>NW</s2>
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<s2>NW</s2>
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<fC07 i1="07" i2="X" l="SPA"><s0>Rodentia</s0>
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<s2>NS</s2>
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<s2>NS</s2>
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<s2>NS</s2>
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<fC07 i1="09" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
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<s2>NS</s2>
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<fC07 i1="10" i2="X" l="FRE"><s0>Dérivé de la phénothiazine</s0>
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<fC07 i1="10" i2="X" l="SPA"><s0>Fenotiazina derivado</s0>
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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

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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