In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine
Identifieur interne : 005294 ( Main/Exploration ); précédent : 005293; suivant : 005295In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine
Auteurs : Els Keyaerts ; Leen Vijgen ; Piet Maes ; Johan Neyts ; Marc Van RanstSource :
- Biochemical and Biophysical Research Communications [ 0006-291X ] ; 2004.
Descripteurs français
- KwdFr :
- ARN complémentaire (métabolisme), Animaux, Antipaludiques (pharmacologie), Antiviraux (pharmacologie), Cellules Vero, Chloroquine (pharmacologie), Concentration inhibitrice 50, Facteurs temps, Humains, RT-PCR, Relation dose-effet des médicaments, Réplication virale, Syndrome respiratoire aigu sévère (traitement médicamenteux), Virus du SRAS (métabolisme).
- MESH :
- métabolisme : ARN complémentaire, Virus du SRAS.
- pharmacologie : Antipaludiques, Antiviraux, Chloroquine.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- Animaux, Cellules Vero, Concentration inhibitrice 50, Facteurs temps, Humains, RT-PCR, Relation dose-effet des médicaments, Réplication virale.
English descriptors
- KwdEn :
- Animals, Antimalarials (pharmacology), Antiviral Agents (pharmacology), Chlorocebus aethiops, Chloroquine (pharmacology), Dose-Response Relationship, Drug, Humans, Inhibitory Concentration 50, RNA, Complementary (metabolism), Reverse Transcriptase Polymerase Chain Reaction, SARS Virus (metabolism), Severe Acute Respiratory Syndrome (drug therapy), Time Factors, Vero Cells, Virus Replication.
- MESH :
- chemical , metabolism : RNA, Complementary.
- chemical , pharmacology : Antimalarials, Antiviral Agents, Chloroquine.
- drug therapy : Severe Acute Respiratory Syndrome.
- metabolism : SARS Virus.
- Animals, Chlorocebus aethiops, Dose-Response Relationship, Drug, Humans, Inhibitory Concentration 50, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Vero Cells, Virus Replication.
Abstract
We report on chloroquine, a 4-amino-quinoline, as an effective inhibitor of the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro. Chloroquine is a clinically approved drug effective against malaria. We tested chloroquine phosphate for its antiviral potential against SARS-CoV-induced cytopathicity in Vero E6 cell culture. Results indicate that the IC50 of chloroquine for antiviral activity (8.8 ± 1.2 μM) was significantly lower than its cytostatic activity; CC50 (261.3 ± 14.5 μM), yielding a selectivity index of 30. The IC50 of chloroquine for inhibition of SARS-CoV in vitro approximates the plasma concentrations of chloroquine reached during treatment of acute malaria. Addition of chloroquine to infected cultures could be delayed for up to 5 h postinfection, without an important drop in antiviral activity. Chloroquine, an old antimalarial drug, may be considered for immediate use in the prevention and treatment of SARS-CoV infections.
Url:
DOI: 10.1016/j.bbrc.2004.08.085
PubMed: 15351731
PubMed Central: 7092815
Affiliations:
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Le document en format XML
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sortKey="Maes, Piet" sort="Maes, Piet" uniqKey="Maes P" first="Piet" last="Maes">Piet Maes</name></author><author><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name></author><author><name sortKey="Ranst, Marc Van" sort="Ranst, Marc Van" uniqKey="Ranst M" first="Marc Van" last="Ranst">Marc Van Ranst</name></author></analytic><series><title level="j">Biochemical and Biophysical Research Communications</title><idno type="ISSN">0006-291X</idno><idno type="eISSN">1090-2104</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antimalarials (pharmacology)</term><term>Antiviral Agents (pharmacology)</term><term>Chlorocebus aethiops</term><term>Chloroquine (pharmacology)</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>RNA, Complementary (metabolism)</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (drug therapy)</term><term>Time Factors</term><term>Vero Cells</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN complémentaire (métabolisme)</term><term>Animaux</term><term>Antipaludiques (pharmacologie)</term><term>Antiviraux (pharmacologie)</term><term>Cellules Vero</term><term>Chloroquine (pharmacologie)</term><term>Concentration inhibitrice 50</term><term>Facteurs temps</term><term>Humains</term><term>RT-PCR</term><term>Relation dose-effet des médicaments</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Complementary</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antimalarials</term><term>Antiviral Agents</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN complémentaire</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antipaludiques</term><term>Antiviraux</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Time Factors</term><term>Vero Cells</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Concentration inhibitrice 50</term><term>Facteurs temps</term><term>Humains</term><term>RT-PCR</term><term>Relation dose-effet des médicaments</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We report on chloroquine, a 4-amino-quinoline, as an effective inhibitor of the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro. Chloroquine is a clinically approved drug effective against malaria. We tested chloroquine phosphate for its antiviral potential against SARS-CoV-induced cytopathicity in Vero E6 cell culture. Results indicate that the IC<sub>50</sub> of chloroquine for antiviral activity (8.8 ± 1.2 μM) was significantly lower than its cytostatic activity; CC<sub>50</sub> (261.3 ± 14.5 μM), yielding a selectivity index of 30. The IC<sub>50</sub> of chloroquine for inhibition of SARS-CoV in vitro approximates the plasma concentrations of chloroquine reached during treatment of acute malaria. Addition of chloroquine to infected cultures could be delayed for up to 5 h postinfection, without an important drop in antiviral activity. Chloroquine, an old antimalarial drug, may be considered for immediate use in the prevention and treatment of SARS-CoV infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S. Gunther</name></author><author><name sortKey="Preiser, W" uniqKey="Preiser W">W. Preiser</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S. van der Werf</name></author><author><name sortKey="Brodt, H R" uniqKey="Brodt H">H.R. Brodt</name></author><author><name sortKey="Becker, S" uniqKey="Becker S">S. Becker</name></author><author><name sortKey="Rabenau, H" uniqKey="Rabenau H">H. Rabenau</name></author><author><name sortKey="Panning, M" uniqKey="Panning M">M. Panning</name></author><author><name sortKey="Kolesnikova, L" uniqKey="Kolesnikova L">L. 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Laurell</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Keyaerts, Els" sort="Keyaerts, Els" uniqKey="Keyaerts E" first="Els" last="Keyaerts">Els Keyaerts</name><name sortKey="Maes, Piet" sort="Maes, Piet" uniqKey="Maes P" first="Piet" last="Maes">Piet Maes</name><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name><name sortKey="Ranst, Marc Van" sort="Ranst, Marc Van" uniqKey="Ranst M" first="Marc Van" last="Ranst">Marc Van Ranst</name><name sortKey="Vijgen, Leen" sort="Vijgen, Leen" uniqKey="Vijgen L" first="Leen" last="Vijgen">Leen Vijgen</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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