SrasV1, PascalFrancis, Corpus, bibRecord, 000120

Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

Identifieur interne : 000120 ( PascalFrancis/Corpus ); précédent : 000119; suivant : 000121

Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

Auteurs : Cheng-Wei Yang ; Yue-Zhi Lee ; Iou-Jiun Kang ; Dale L. Bamard ; Jia-Tsrong Jan ; DU LIN ; Chun-Wei Huang ; Teng-Kuang Yeh ; Yu-Sheng Chao ; Shiow-Ju Lee

Source :

Antiviral research [ 0166-3542 ] ; 2010.

RBID : Pascal:11-0057292

Descripteurs français

Pascal (Inist)
- Antiviral, Isolement, Relation structure activité, Alcaloïde, Virus gastroentérite transmissible porcin, Cryptopleurine, Syndrome respiratoire aigu sévère, Asclepiadaceae, Origine végétale, Plante médicinale, Urticaceae, Souche entéropathogène, Tylophorine, Tylophora, Boehmeria siamensis.

English descriptors

KwdEn :
- Alkaloid, Antiviral, Asclepiadaceae, Isolation, Medicinal plant, Plant origin, Porcine transmissible gastroenteritis virus, Severe acute respiratory syndrome, Structure activity relation, Urticaceae.

Abstract

The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC_so) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS CoV), with EC₅₀ values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS CoV infection.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A14	`02`			`@1 Institute of Molecular Medicine, National Tsing Hua University @2 Hsinchu @3 TWN @Z 1 aut.`
A14	`03`			`@1 Institute forAntiviral Research, Utah State University @2 Logan, UT @3 USA @Z 4 aut.`
A14	`04`			`@1 Genomics Research Center, Academia Sinica @3 TWN @Z 5 aut.`
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C01	`01`		`ENG`	@0 The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC_so) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS CoV), with EC₅₀ values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS CoV infection.
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Format Inist (serveur)

NO :	PASCAL 11-0057292 INIST
ET :	Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus
AU :	YANG (Cheng-Wei); LEE (Yue-Zhi); KANG (Iou-Jiun); BAMARD (Dale L.); JAN (Jia-Tsrong); DU LIN; HUANG (Chun-Wei); YEH (Teng-Kuang); CHAO (Yu-Sheng); LEE (Shiow-Ju)
AF :	Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes/Miaoli/Taïwan (1 aut., 2 aut., 3 aut., 6 aut., 7 aut., 8 aut., 9 aut., 10 aut.); Institute of Molecular Medicine, National Tsing Hua University/Hsinchu/Taïwan (1 aut.); Institute forAntiviral Research, Utah State University/Logan, UT/Etats-Unis (4 aut.); Genomics Research Center, Academia Sinica/Taïwan (5 aut.)
DT :	Publication en série; Niveau analytique
SO :	Antiviral research; ISSN 0166-3542; Coden ARSRDR; Royaume-Uni; Da. 2010; Vol. 88; No. 2; Pp. 160-168; Bibl. 3/4 p.
LA :	Anglais
EA :	The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC_so) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS CoV), with EC₅₀ values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS CoV infection.
CC :	002B02S05
FD :	Antiviral; Isolement; Relation structure activité; Alcaloïde; Virus gastroentérite transmissible porcin; Cryptopleurine; Syndrome respiratoire aigu sévère; Asclepiadaceae; Origine végétale; Plante médicinale; Urticaceae; Souche entéropathogène; Tylophorine; Tylophora; Boehmeria siamensis
FG :	Coronavirus; Coronaviridae; Nidovirales; Virus; Virose; Infection; Dicotyledones; Angiospermae; Spermatophyta; Pathologie de l'appareil respiratoire; Pathologie des poumons; Pharmacognosie
ED :	Antiviral; Isolation; Structure activity relation; Alkaloid; Porcine transmissible gastroenteritis virus; Severe acute respiratory syndrome; Asclepiadaceae; Plant origin; Medicinal plant; Urticaceae
EG :	Coronavirus; Coronaviridae; Nidovirales; Virus; Viral disease; Infection; Dicotyledones; Angiospermae; Spermatophyta; Respiratory disease; Lung disease; Pharmacognosy
SD :	Antiviral; Aislamiento; Relación estructura actividad; Alcaloide; Porcine transmissible gastroenteritis virus; Síndrome respiratorio agudo severo; Asclepiadaceae; Origen vegetal; Planta medicinal; Urticaceae
LO :	INIST-18839.354000193946920040
ID :	11-0057292

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Pascal:11-0057292

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus</title>
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</author>
<author><name sortKey="Lee, Yue Zhi" sort="Lee, Yue Zhi" uniqKey="Lee Y" first="Yue-Zhi" last="Lee">Yue-Zhi Lee</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Kang, Iou Jiun" sort="Kang, Iou Jiun" uniqKey="Kang I" first="Iou-Jiun" last="Kang">Iou-Jiun Kang</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Bamard, Dale L" sort="Bamard, Dale L" uniqKey="Bamard D" first="Dale L." last="Bamard">Dale L. Bamard</name>
<affiliation><inist:fA14 i1="03"><s1>Institute forAntiviral Research, Utah State University</s1>
<s2>Logan, UT</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Jan, Jia Tsrong" sort="Jan, Jia Tsrong" uniqKey="Jan J" first="Jia-Tsrong" last="Jan">Jia-Tsrong Jan</name>
<affiliation><inist:fA14 i1="04"><s1>Genomics Research Center, Academia Sinica</s1>
<s3>TWN</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Du Lin" sort="Du Lin" uniqKey="Du Lin" last="Du Lin">DU LIN</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Huang, Chun Wei" sort="Huang, Chun Wei" uniqKey="Huang C" first="Chun-Wei" last="Huang">Chun-Wei Huang</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Yeh, Teng Kuang" sort="Yeh, Teng Kuang" uniqKey="Yeh T" first="Teng-Kuang" last="Yeh">Teng-Kuang Yeh</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Chao, Yu Sheng" sort="Chao, Yu Sheng" uniqKey="Chao Y" first="Yu-Sheng" last="Chao">Yu-Sheng Chao</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Lee, Shiow Ju" sort="Lee, Shiow Ju" uniqKey="Lee S" first="Shiow-Ju" last="Lee">Shiow-Ju Lee</name>
<affiliation><inist:fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</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="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<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>Alkaloid</term>
<term>Antiviral</term>
<term>Asclepiadaceae</term>
<term>Isolation</term>
<term>Medicinal plant</term>
<term>Plant origin</term>
<term>Porcine transmissible gastroenteritis virus</term>
<term>Severe acute respiratory syndrome</term>
<term>Structure activity relation</term>
<term>Urticaceae</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Antiviral</term>
<term>Isolement</term>
<term>Relation structure activité</term>
<term>Alcaloïde</term>
<term>Virus gastroentérite transmissible porcin</term>
<term>Cryptopleurine</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Asclepiadaceae</term>
<term>Origine végétale</term>
<term>Plante médicinale</term>
<term>Urticaceae</term>
<term>Souche entéropathogène</term>
<term>Tylophorine</term>
<term>Tylophora</term>
<term>Boehmeria siamensis</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC<sub>so</sub>
) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS CoV), with EC<sub>50</sub>
 values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS CoV infection.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0166-3542</s0>
</fA01>
<fA02 i1="01"><s0>ARSRDR</s0>
</fA02>
<fA03 i2="1"><s0>Antivir. res.</s0>
</fA03>
<fA05><s2>88</s2>
</fA05>
<fA06><s2>2</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>YANG (Cheng-Wei)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>LEE (Yue-Zhi)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>KANG (Iou-Jiun)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>BAMARD (Dale L.)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>JAN (Jia-Tsrong)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>DU LIN</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>HUANG (Chun-Wei)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>YEH (Teng-Kuang)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>CHAO (Yu-Sheng)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>LEE (Shiow-Ju)</s1>
</fA11>
<fA14 i1="01"><s1>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes</s1>
<s2>Miaoli</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Institute of Molecular Medicine, National Tsing Hua University</s1>
<s2>Hsinchu</s2>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Institute forAntiviral Research, Utah State University</s1>
<s2>Logan, UT</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Genomics Research Center, Academia Sinica</s1>
<s3>TWN</s3>
<sZ>5 aut.</sZ>
</fA14>
<fA20><s1>160-168</s1>
</fA20>
<fA21><s1>2010</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>18839</s2>
<s5>354000193946920040</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2011 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>3/4 p.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>11-0057292</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Antiviral research</s0>
</fA64>
<fA66 i1="01"><s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC<sub>so</sub>
) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS CoV), with EC<sub>50</sub>
 values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS CoV infection.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Antiviral</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Antiviral</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Isolement</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Isolation</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Aislamiento</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Relation structure activité</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Structure activity relation</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Relación estructura actividad</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Alcaloïde</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Alkaloid</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Alcaloide</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Virus gastroentérite transmissible porcin</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Porcine transmissible gastroenteritis virus</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Porcine transmissible gastroenteritis virus</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Cryptopleurine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0>
<s2>NM</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0>
<s2>NM</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0>
<s2>NM</s2>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Asclepiadaceae</s0>
<s2>NS</s2>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Asclepiadaceae</s0>
<s2>NS</s2>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Asclepiadaceae</s0>
<s2>NS</s2>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Origine végétale</s0>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Plant origin</s0>
<s5>10</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Origen vegetal</s0>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Plante médicinale</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Medicinal plant</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Planta medicinal</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Urticaceae</s0>
<s2>NS</s2>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Urticaceae</s0>
<s2>NS</s2>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Urticaceae</s0>
<s2>NS</s2>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Souche entéropathogène</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Tylophorine</s0>
<s4>INC</s4>
<s5>87</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Tylophora</s0>
<s4>INC</s4>
<s5>88</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE"><s0>Boehmeria siamensis</s0>
<s4>INC</s4>
<s5>89</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Virose</s0>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Viral disease</s0>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Virosis</s0>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Infection</s0>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Infection</s0>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Infección</s0>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Dicotyledones</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Dicotyledones</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Dicotyledones</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Angiospermae</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Angiospermae</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Angiospermae</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Spermatophyta</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Spermatophyta</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Spermatophyta</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0>
<s5>37</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Respiratory disease</s0>
<s5>37</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="11" i2="X" l="FRE"><s0>Pathologie des poumons</s0>
<s5>38</s5>
</fC07>
<fC07 i1="11" i2="X" l="ENG"><s0>Lung disease</s0>
<s5>38</s5>
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<ET>Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus</ET>
<AU>YANG (Cheng-Wei); LEE (Yue-Zhi); KANG (Iou-Jiun); BAMARD (Dale L.); JAN (Jia-Tsrong); DU LIN; HUANG (Chun-Wei); YEH (Teng-Kuang); CHAO (Yu-Sheng); LEE (Shiow-Ju)</AU>
<AF>Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes/Miaoli/Taïwan (1 aut., 2 aut., 3 aut., 6 aut., 7 aut., 8 aut., 9 aut., 10 aut.); Institute of Molecular Medicine, National Tsing Hua University/Hsinchu/Taïwan (1 aut.); Institute forAntiviral Research, Utah State University/Logan, UT/Etats-Unis (4 aut.); Genomics Research Center, Academia Sinica/Taïwan (5 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Antiviral research; ISSN 0166-3542; Coden ARSRDR; Royaume-Uni; Da. 2010; Vol. 88; No. 2; Pp. 160-168; Bibl. 3/4 p.</SO>
<LA>Anglais</LA>
<EA>The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC<sub>so</sub>
) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS CoV), with EC<sub>50</sub>
 values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS CoV infection.</EA>
<CC>002B02S05</CC>
<FD>Antiviral; Isolement; Relation structure activité; Alcaloïde; Virus gastroentérite transmissible porcin; Cryptopleurine; Syndrome respiratoire aigu sévère; Asclepiadaceae; Origine végétale; Plante médicinale; Urticaceae; Souche entéropathogène; Tylophorine; Tylophora; Boehmeria siamensis</FD>
<FG>Coronavirus; Coronaviridae; Nidovirales; Virus; Virose; Infection; Dicotyledones; Angiospermae; Spermatophyta; Pathologie de l'appareil respiratoire; Pathologie des poumons; Pharmacognosie</FG>
<ED>Antiviral; Isolation; Structure activity relation; Alkaloid; Porcine transmissible gastroenteritis virus; Severe acute respiratory syndrome; Asclepiadaceae; Plant origin; Medicinal plant; Urticaceae</ED>
<EG>Coronavirus; Coronaviridae; Nidovirales; Virus; Viral disease; Infection; Dicotyledones; Angiospermae; Spermatophyta; Respiratory disease; Lung disease; Pharmacognosy</EG>
<SD>Antiviral; Aislamiento; Relación estructura actividad; Alcaloide; Porcine transmissible gastroenteritis virus; Síndrome respiratorio agudo severo; Asclepiadaceae; Origen vegetal; Planta medicinal; Urticaceae</SD>
<LO>INIST-18839.354000193946920040</LO>
<ID>11-0057292</ID>
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Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

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