SrasV1, Main, Exploration, bibRecord, 004439

Indomethacin has a potent antiviral activity against SARS coronavirus

Identifieur interne : 004439 ( Main/Exploration ); précédent : 004438; suivant : 004440

Indomethacin has a potent antiviral activity against SARS coronavirus

Auteurs : Carla Amici [Italie] ; Antonino Di Caro [Italie] ; Alessandra Ciucci [Italie] ; Lucia Chiappa [Italie] ; Concetta Castilletti [Italie] ; Vito Martella [Italie] ; Nicola Decaro [Italie] ; Canio Buonavoglia [Italie] ; Maria R. Capobianchi [Italie] ; M. Gabriella Santoro [Italie]

Source :

Antiviral therapy : (London) [ 1359-6535 ] ; 2006.

RBID : Pascal:07-0058292

Descripteurs français

KwdFr :
- ARN viral (isolement et purification), Acide acétylsalicylique (pharmacologie), Animaux, Antiviraux (pharmacologie), Antiviraux (usage thérapeutique), Chiens, Coronavirus canin (), Fèces (virologie), Humains, Indométacine (pharmacologie), Indométacine (usage thérapeutique), Infections à coronavirus (médecine vétérinaire), Infections à coronavirus (traitement médicamenteux), Interféron alpha (pharmacologie), Lignée cellulaire, Maladies des chiens (traitement médicamenteux), Relation dose-effet des médicaments, Ribavirine (pharmacologie), Réplication virale (), Virus du SRAS ().
MESH :
- isolement et purification : ARN viral.
- médecine vétérinaire : Infections à coronavirus.
- pharmacologie : Acide acétylsalicylique, Antiviraux, Indométacine, Interféron alpha, Ribavirine.
- traitement médicamenteux : Infections à coronavirus, Maladies des chiens.
- usage thérapeutique : Antiviraux, Indométacine.
- virologie : Fèces.
Pascal (Inist)
- Animaux, Chiens, Coronavirus canin, Humains, Indométacine, Antiviral, Lignée cellulaire, Relation dose-effet des médicaments, Réplication virale, Virus du SRAS, Virus syndrome respiratoire aigu sévère, Antiinflammatoire non stéroïde, Tocolytique.

English descriptors

KwdEn :
- Animals, Antiviral, Antiviral Agents (pharmacology), Antiviral Agents (therapeutic use), Aspirin (pharmacology), Cell Line, Chlorocebus aethiops, Coronavirus Infections (drug therapy), Coronavirus Infections (veterinary), Coronavirus, Canine (drug effects), Dog Diseases (drug therapy), Dogs, Dose-Response Relationship, Drug, Feces (virology), Humans, Indometacin, Indomethacin (pharmacology), Indomethacin (therapeutic use), Interferon-alpha (pharmacology), Non steroidal antiinflammatory agent, RNA, Viral (isolation & purification), Ribavirin (pharmacology), SARS Virus (drug effects), Severe acute respiratory syndrome virus, Tocolytic, Virus Replication (drug effects).
MESH :
- chemical , isolation & purification : RNA, Viral.
- chemical , pharmacology : Antiviral Agents, Aspirin, Indomethacin, Interferon-alpha, Ribavirin.
- chemical , therapeutic use : Antiviral Agents, Indomethacin.
- drug effects : Coronavirus, Canine, SARS Virus, Virus Replication.
- drug therapy : Coronavirus Infections, Dog Diseases.
- veterinary : Coronavirus Infections.
- virology : Feces.
- Animals, Cell Line, Chlorocebus aethiops, Dogs, Dose-Response Relationship, Drug, Humans.

Abstract

Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. Objectives: Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. Methods: Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID₅₀, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after ³⁵S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). Results: Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. Conclusions: The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.

Affiliations:

Le document en format XML

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<term>Aspirin (pharmacology)</term>
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<term>Indométacine</term>
</keywords>
<keywords scheme="MESH" qualifier="veterinary" xml:lang="en"><term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Fèces</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Feces</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Dogs</term>
<term>Dose-Response Relationship, Drug</term>
<term>Humans</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Chiens</term>
<term>Coronavirus canin</term>
<term>Humains</term>
<term>Indométacine</term>
<term>Antiviral</term>
<term>Lignée cellulaire</term>
<term>Relation dose-effet des médicaments</term>
<term>Réplication virale</term>
<term>Virus du SRAS</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Antiinflammatoire non stéroïde</term>
<term>Tocolytique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. Objectives: Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. Methods: Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID<sub>50</sub>
, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after <sup>35</sup>
S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). Results: Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. Conclusions: The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.</div>
</front>
</TEI>
<affiliations><list><country><li>Italie</li>
</country>
<region><li>Latium</li>
</region>
<settlement><li>Rome</li>
</settlement>
</list>
<tree><country name="Italie"><region name="Latium"><name sortKey="Amici, Carla" sort="Amici, Carla" uniqKey="Amici C" first="Carla" last="Amici">Carla Amici</name>
</region>
<name sortKey="Buonavoglia, Canio" sort="Buonavoglia, Canio" uniqKey="Buonavoglia C" first="Canio" last="Buonavoglia">Canio Buonavoglia</name>
<name sortKey="Capobianchi, Maria R" sort="Capobianchi, Maria R" uniqKey="Capobianchi M" first="Maria R." last="Capobianchi">Maria R. Capobianchi</name>
<name sortKey="Castilletti, Concetta" sort="Castilletti, Concetta" uniqKey="Castilletti C" first="Concetta" last="Castilletti">Concetta Castilletti</name>
<name sortKey="Chiappa, Lucia" sort="Chiappa, Lucia" uniqKey="Chiappa L" first="Lucia" last="Chiappa">Lucia Chiappa</name>
<name sortKey="Ciucci, Alessandra" sort="Ciucci, Alessandra" uniqKey="Ciucci A" first="Alessandra" last="Ciucci">Alessandra Ciucci</name>
<name sortKey="Decaro, Nicola" sort="Decaro, Nicola" uniqKey="Decaro N" first="Nicola" last="Decaro">Nicola Decaro</name>
<name sortKey="Di Caro, Antonino" sort="Di Caro, Antonino" uniqKey="Di Caro A" first="Antonino" last="Di Caro">Antonino Di Caro</name>
<name sortKey="Martella, Vito" sort="Martella, Vito" uniqKey="Martella V" first="Vito" last="Martella">Vito Martella</name>
<name sortKey="Santoro, M Gabriella" sort="Santoro, M Gabriella" uniqKey="Santoro M" first="M. Gabriella" last="Santoro">M. Gabriella Santoro</name>
</country>
</tree>
</affiliations>
</record>

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Indomethacin has a potent antiviral activity against SARS coronavirus

Indomethacin has a potent antiviral activity against SARS coronavirus

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