Repurposing chlorpromazine to treat COVID-19: The reCoVery study.
Identifieur interne : 000759 ( Main/Exploration ); précédent : 000758; suivant : 000760Repurposing chlorpromazine to treat COVID-19: The reCoVery study.
Auteurs : M. Plaze [France] ; D. Attali [France] ; A-C Petit [France] ; M. Blatzer [France] ; E. Simon-Loriere [France] ; F. Vinckier [France] ; A. Cachia [France] ; F. Chrétien [France] ; R. Gaillard [France]Source :
- L'Encephale [ 0013-7006 ] ; 2020.
Descripteurs français
- KwdFr :
- Antiviraux (usage thérapeutique), Anxiété (anatomopathologie), Anxiété (complications), Anxiété (traitement médicamenteux), Anxiété (épidémiologie), Barrière hémato-encéphalique (effets des médicaments et des substances chimiques), Betacoronavirus (pathogénicité), Chlorpromazine (usage thérapeutique), Durée du séjour (MeSH), Dyspnée (anatomopathologie), Dyspnée (psychologie), Dyspnée (traitement médicamenteux), Dyspnée (épidémiologie), Délai jusqu'au traitement (MeSH), Endocytose (effets des médicaments et des substances chimiques), France (épidémiologie), Humains (MeSH), Infections à coronavirus (anatomopathologie), Infections à coronavirus (complications), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (épidémiologie), Mortalité (MeSH), Méthode en simple aveugle (MeSH), Pandémies (MeSH), Pneumopathie virale (anatomopathologie), Pneumopathie virale (complications), Pneumopathie virale (traitement médicamenteux), Pneumopathie virale (épidémiologie), Projets pilotes (MeSH), Repositionnement des médicaments (MeSH), Récupération fonctionnelle (MeSH), Résultat thérapeutique (MeSH), Vésicules tapissées de clathrine (effets des médicaments et des substances chimiques), Évaluation des résultats des patients (MeSH), Évolution de la maladie (MeSH).
- MESH :
- anatomopathologie : Anxiété, Dyspnée, Infections à coronavirus, Pneumopathie virale.
- effets des médicaments et des substances chimiques : Barrière hémato-encéphalique, Endocytose, Vésicules tapissées de clathrine.
- pathogénicité : Betacoronavirus.
- psychologie : Dyspnée.
- traitement médicamenteux : Anxiété, Dyspnée, Infections à coronavirus, Pneumopathie virale.
- usage thérapeutique : Antiviraux, Anxiété, Chlorpromazine, Infections à coronavirus, Pneumopathie virale.
- épidémiologie : Anxiété, Dyspnée, France, Infections à coronavirus, Pneumopathie virale.
- Durée du séjour, Délai jusqu'au traitement, Humains, Mortalité, Méthode en simple aveugle, Pandémies, Projets pilotes, Repositionnement des médicaments, Récupération fonctionnelle, Résultat thérapeutique, Évaluation des résultats des patients, Évolution de la maladie.
- Wicri :
- geographic : France.
English descriptors
- KwdEn :
- Antiviral Agents (therapeutic use), Anxiety (complications), Anxiety (drug therapy), Anxiety (epidemiology), Anxiety (pathology), Betacoronavirus (pathogenicity), Blood-Brain Barrier (drug effects), Chlorpromazine (therapeutic use), Clathrin-Coated Vesicles (drug effects), Coronavirus Infections (complications), Coronavirus Infections (drug therapy), Coronavirus Infections (epidemiology), Coronavirus Infections (pathology), Disease Progression (MeSH), Drug Repositioning (MeSH), Dyspnea (drug therapy), Dyspnea (epidemiology), Dyspnea (pathology), Dyspnea (psychology), Endocytosis (drug effects), France (epidemiology), Humans (MeSH), Length of Stay (MeSH), Mortality (MeSH), Pandemics (MeSH), Patient Outcome Assessment (MeSH), Pilot Projects (MeSH), Pneumonia, Viral (complications), Pneumonia, Viral (drug therapy), Pneumonia, Viral (epidemiology), Pneumonia, Viral (pathology), Recovery of Function (MeSH), Single-Blind Method (MeSH), Time-to-Treatment (MeSH), Treatment Outcome (MeSH).
- MESH :
- chemical , therapeutic use : Antiviral Agents, Chlorpromazine.
- geographic , epidemiology : France.
- complications : Anxiety, Coronavirus Infections, Pneumonia, Viral.
- drug effects : Blood-Brain Barrier, Clathrin-Coated Vesicles, Endocytosis.
- drug therapy : Anxiety, Coronavirus Infections, Dyspnea, Pneumonia, Viral.
- epidemiology : Anxiety, Coronavirus Infections, Dyspnea, Pneumonia, Viral.
- pathogenicity : Betacoronavirus.
- pathology : Anxiety, Coronavirus Infections, Dyspnea, Pneumonia, Viral.
- psychology : Dyspnea.
- Disease Progression, Drug Repositioning, Humans, Length of Stay, Mortality, Pandemics, Patient Outcome Assessment, Pilot Projects, Recovery of Function, Single-Blind Method, Time-to-Treatment, Treatment Outcome.
Abstract
OBJECTIVES
The ongoing COVID-19 pandemic has caused approximately 2,350,000 infections worldwide and killed more than 160,000 individuals. In Sainte-Anne Hospital (GHU PARIS Psychiatrie & Neuroscience, Paris, France) we have observed a lower incidence of symptomatic forms of COVID-19 among patients than among our clinical staff. This observation led us to hypothesize that psychotropic drugs could have a prophylactic action against SARS-CoV-2 and protect patients from the symptomatic and virulent forms of this infection, since several of these psychotropic drugs have documented antiviral properties. Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. Recentin vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity.
METHODS
In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. For this purpose, we plan a pilot, multicenter, randomized, single blind, controlled, phase III therapeutic trial (standard treatment vs. CPZ+standard treatment).
CONCLUSION
This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. This repurposing strategy also avoids numerous developmental and experimental steps, and could save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easily managed side effects.
DOI: 10.1016/j.encep.2020.05.006
PubMed: 32425222
PubMed Central: PMC7229964
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Simon-Loriere</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, G5 Evolutionary Genomics of RNA Viruses, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, G5 Evolutionary Genomics of RNA Viruses, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vinckier, F" sort="Vinckier, F" uniqKey="Vinckier F" first="F" last="Vinckier">F. Vinckier</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Cachia, A" sort="Cachia, A" uniqKey="Cachia A" first="A" last="Cachia">A. Cachia</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, Paris, France; Université de Paris, Laboratoire de Psychologie du développement et de l'Éducation de l'Enfant, CNRS, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, Paris, France; Université de Paris, Laboratoire de Psychologie du développement et de l'Éducation de l'Enfant, CNRS, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chretien, F" sort="Chretien, F" uniqKey="Chretien F" first="F" last="Chrétien">F. Chrétien</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Experimental Neuropathology Unit, Paris, France; GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service de Neuropathologie, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Experimental Neuropathology Unit, Paris, France; GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service de Neuropathologie, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gaillard, R" sort="Gaillard, R" uniqKey="Gaillard R" first="R" last="Gaillard">R. Gaillard</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32425222</idno><idno type="pmid">32425222</idno><idno type="doi">10.1016/j.encep.2020.05.006</idno><idno type="pmc">PMC7229964</idno><idno type="wicri:Area/Main/Corpus">001222</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001222</idno><idno type="wicri:Area/Main/Curation">001222</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001222</idno><idno type="wicri:Area/Main/Exploration">001222</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Repurposing chlorpromazine to treat COVID-19: The reCoVery study.</title><author><name sortKey="Plaze, M" sort="Plaze, M" uniqKey="Plaze M" first="M" last="Plaze">M. Plaze</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France. Electronic address: m.plaze@ghu-paris.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Attali, D" sort="Attali, D" uniqKey="Attali D" first="D" last="Attali">D. Attali</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Univ Paris Diderot, Sorbonne Paris Cite, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Petit, A C" sort="Petit, A C" uniqKey="Petit A" first="A-C" last="Petit">A-C Petit</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Blatzer, M" sort="Blatzer, M" uniqKey="Blatzer M" first="M" last="Blatzer">M. Blatzer</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Experimental Neuropathology Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Simon Loriere, E" sort="Simon Loriere, E" uniqKey="Simon Loriere E" first="E" last="Simon-Loriere">E. Simon-Loriere</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, G5 Evolutionary Genomics of RNA Viruses, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, G5 Evolutionary Genomics of RNA Viruses, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vinckier, F" sort="Vinckier, F" uniqKey="Vinckier F" first="F" last="Vinckier">F. Vinckier</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Cachia, A" sort="Cachia, A" uniqKey="Cachia A" first="A" last="Cachia">A. Cachia</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, Paris, France; Université de Paris, Laboratoire de Psychologie du développement et de l'Éducation de l'Enfant, CNRS, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, Paris, France; Université de Paris, Laboratoire de Psychologie du développement et de l'Éducation de l'Enfant, CNRS, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Chretien, F" sort="Chretien, F" uniqKey="Chretien F" first="F" last="Chrétien">F. Chrétien</name><affiliation wicri:level="3"><nlm:affiliation>Institut Pasteur, Experimental Neuropathology Unit, Paris, France; GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service de Neuropathologie, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Experimental Neuropathology Unit, Paris, France; GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service de Neuropathologie, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gaillard, R" sort="Gaillard, R" uniqKey="Gaillard R" first="R" last="Gaillard">R. Gaillard</name><affiliation wicri:level="3"><nlm:affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">L'Encephale</title><idno type="ISSN">0013-7006</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (therapeutic use)</term><term>Anxiety (complications)</term><term>Anxiety (drug therapy)</term><term>Anxiety (epidemiology)</term><term>Anxiety (pathology)</term><term>Betacoronavirus (pathogenicity)</term><term>Blood-Brain Barrier (drug effects)</term><term>Chlorpromazine (therapeutic use)</term><term>Clathrin-Coated Vesicles (drug effects)</term><term>Coronavirus Infections (complications)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (epidemiology)</term><term>Coronavirus Infections (pathology)</term><term>Disease Progression (MeSH)</term><term>Drug Repositioning (MeSH)</term><term>Dyspnea (drug therapy)</term><term>Dyspnea (epidemiology)</term><term>Dyspnea (pathology)</term><term>Dyspnea (psychology)</term><term>Endocytosis (drug effects)</term><term>France (epidemiology)</term><term>Humans (MeSH)</term><term>Length of Stay (MeSH)</term><term>Mortality (MeSH)</term><term>Pandemics (MeSH)</term><term>Patient Outcome Assessment (MeSH)</term><term>Pilot Projects (MeSH)</term><term>Pneumonia, Viral (complications)</term><term>Pneumonia, Viral (drug therapy)</term><term>Pneumonia, Viral (epidemiology)</term><term>Pneumonia, Viral (pathology)</term><term>Recovery of Function (MeSH)</term><term>Single-Blind Method (MeSH)</term><term>Time-to-Treatment (MeSH)</term><term>Treatment Outcome (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux (usage thérapeutique)</term><term>Anxiété (anatomopathologie)</term><term>Anxiété (complications)</term><term>Anxiété (traitement médicamenteux)</term><term>Anxiété (épidémiologie)</term><term>Barrière hémato-encéphalique (effets des médicaments et des substances chimiques)</term><term>Betacoronavirus (pathogénicité)</term><term>Chlorpromazine (usage thérapeutique)</term><term>Durée du séjour (MeSH)</term><term>Dyspnée (anatomopathologie)</term><term>Dyspnée (psychologie)</term><term>Dyspnée (traitement médicamenteux)</term><term>Dyspnée (épidémiologie)</term><term>Délai jusqu'au traitement (MeSH)</term><term>Endocytose (effets des médicaments et des substances chimiques)</term><term>France (épidémiologie)</term><term>Humains (MeSH)</term><term>Infections à coronavirus (anatomopathologie)</term><term>Infections à coronavirus (complications)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (épidémiologie)</term><term>Mortalité (MeSH)</term><term>Méthode en simple aveugle (MeSH)</term><term>Pandémies (MeSH)</term><term>Pneumopathie virale (anatomopathologie)</term><term>Pneumopathie virale (complications)</term><term>Pneumopathie virale (traitement médicamenteux)</term><term>Pneumopathie virale (épidémiologie)</term><term>Projets pilotes (MeSH)</term><term>Repositionnement des médicaments (MeSH)</term><term>Récupération fonctionnelle (MeSH)</term><term>Résultat thérapeutique (MeSH)</term><term>Vésicules tapissées de clathrine (effets des médicaments et des substances chimiques)</term><term>Évaluation des résultats des patients (MeSH)</term><term>Évolution de la maladie (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Chlorpromazine</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>France</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Anxiété</term><term>Dyspnée</term><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Anxiety</term><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood-Brain Barrier</term><term>Clathrin-Coated Vesicles</term><term>Endocytosis</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Anxiety</term><term>Coronavirus Infections</term><term>Dyspnea</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Barrière hémato-encéphalique</term><term>Endocytose</term><term>Vésicules tapissées de clathrine</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Anxiety</term><term>Coronavirus Infections</term><term>Dyspnea</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Anxiety</term><term>Coronavirus Infections</term><term>Dyspnea</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="psychologie" xml:lang="fr"><term>Dyspnée</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Dyspnea</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Anxiété</term><term>Dyspnée</term><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antiviraux</term><term>Anxiété</term><term>Chlorpromazine</term><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Anxiété</term><term>Dyspnée</term><term>France</term><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Disease Progression</term><term>Drug Repositioning</term><term>Humans</term><term>Length of Stay</term><term>Mortality</term><term>Pandemics</term><term>Patient Outcome Assessment</term><term>Pilot Projects</term><term>Recovery of Function</term><term>Single-Blind Method</term><term>Time-to-Treatment</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Durée du séjour</term><term>Délai jusqu'au traitement</term><term>Humains</term><term>Mortalité</term><term>Méthode en simple aveugle</term><term>Pandémies</term><term>Projets pilotes</term><term>Repositionnement des médicaments</term><term>Récupération fonctionnelle</term><term>Résultat thérapeutique</term><term>Évaluation des résultats des patients</term><term>Évolution de la maladie</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>France</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVES</b></p><p>The ongoing COVID-19 pandemic has caused approximately 2,350,000 infections worldwide and killed more than 160,000 individuals. In Sainte-Anne Hospital (GHU PARIS Psychiatrie & Neuroscience, Paris, France) we have observed a lower incidence of symptomatic forms of COVID-19 among patients than among our clinical staff. This observation led us to hypothesize that psychotropic drugs could have a prophylactic action against SARS-CoV-2 and protect patients from the symptomatic and virulent forms of this infection, since several of these psychotropic drugs have documented antiviral properties. Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. Recentin vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. For this purpose, we plan a pilot, multicenter, randomized, single blind, controlled, phase III therapeutic trial (standard treatment vs. CPZ+standard treatment).</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. This repurposing strategy also avoids numerous developmental and experimental steps, and could save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easily managed side effects.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32425222</PMID><DateCompleted><Year>2020</Year><Month>06</Month><Day>24</Day></DateCompleted><DateRevised><Year>2020</Year><Month>06</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0013-7006</ISSN><JournalIssue CitedMedium="Internet"><Volume>46</Volume><Issue>3</Issue><PubDate><Year>2020</Year><Month>Jun</Month></PubDate></JournalIssue><Title>L'Encephale</Title><ISOAbbreviation>Encephale</ISOAbbreviation></Journal><ArticleTitle>Repurposing chlorpromazine to treat COVID-19: The reCoVery study.</ArticleTitle><Pagination><MedlinePgn>169-172</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0013-7006(20)30091-9</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.encep.2020.05.006</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">The ongoing COVID-19 pandemic has caused approximately 2,350,000 infections worldwide and killed more than 160,000 individuals. In Sainte-Anne Hospital (GHU PARIS Psychiatrie & Neuroscience, Paris, France) we have observed a lower incidence of symptomatic forms of COVID-19 among patients than among our clinical staff. This observation led us to hypothesize that psychotropic drugs could have a prophylactic action against SARS-CoV-2 and protect patients from the symptomatic and virulent forms of this infection, since several of these psychotropic drugs have documented antiviral properties. Chlorpromazine (CPZ), a phenothiazine derivative, is also known for its antiviral activity via the inhibition of clathrin-mediated endocytosis. Recentin vitro studies have reported that CPZ exhibits anti-MERS-CoV and anti-SARS-CoV-1 activity.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">In this context, the ReCoVery study aims to repurpose CPZ, a molecule with an excellent tolerance profile and a very high biodistribution in the saliva, lungs and brain. We hypothesize that CPZ could reduce the unfavorable course of COVID-19 infection among patients requiring respiratory support without the need for ICU care, and that it could also reduce the contagiousness of SARS-CoV-2. For this purpose, we plan a pilot, multicenter, randomized, single blind, controlled, phase III therapeutic trial (standard treatment vs. CPZ+standard treatment).</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">This repurposing of CPZ for its anti-SARS-CoV-2 activity could offer an alternative, rapid strategy to alleviate infection severity. This repurposing strategy also avoids numerous developmental and experimental steps, and could save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easily managed side effects.</AbstractText><CopyrightInformation>Copyright © 2020 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Plaze</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France. Electronic address: m.plaze@ghu-paris.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Attali</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petit</LastName><ForeName>A-C</ForeName><Initials>AC</Initials><AffiliationInfo><Affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blatzer</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Simon-Loriere</LastName><ForeName>E</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Institut Pasteur, G5 Evolutionary Genomics of RNA Viruses, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vinckier</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cachia</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, Paris, France; Université de Paris, Laboratoire de Psychologie du développement et de l'Éducation de l'Enfant, CNRS, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chrétien</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Experimental Neuropathology Unit, Paris, France; GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service de Neuropathologie, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gaillard</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, Pôle Hospitalo-Universitaire Paris 15, Paris, France; Université de Paris, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D017428">Clinical Trial, Phase III</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>05</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Encephale</MedlineTA><NlmUniqueID>7505643</NlmUniqueID><ISSNLinking>0013-7006</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>U42B7VYA4P</RegistryNumber><NameOfSubstance UI="D002746">Chlorpromazine</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001007" MajorTopicYN="N">Anxiety</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName><QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001812" MajorTopicYN="N">Blood-Brain Barrier</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002746" MajorTopicYN="N">Chlorpromazine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D022163" MajorTopicYN="N">Clathrin-Coated Vesicles</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018450" MajorTopicYN="N">Disease Progression</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058492" MajorTopicYN="Y">Drug Repositioning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004417" MajorTopicYN="N">Dyspnea</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000523" MajorTopicYN="N">psychology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004705" MajorTopicYN="N">Endocytosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005602" MajorTopicYN="N" Type="Geographic">France</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007902" MajorTopicYN="N">Length of Stay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009026" MajorTopicYN="N">Mortality</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D063868" MajorTopicYN="N">Patient Outcome Assessment</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010865" MajorTopicYN="N">Pilot Projects</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020127" MajorTopicYN="N">Recovery of Function</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016037" MajorTopicYN="N">Single-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061665" MajorTopicYN="N">Time-to-Treatment</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Chlorpromazine</Keyword><Keyword MajorTopicYN="N">Clinical trial</Keyword><Keyword MajorTopicYN="N">Essai clinique</Keyword><Keyword MajorTopicYN="N">Repositionnement de molécules</Keyword><Keyword MajorTopicYN="N">Repurposing of molecules</Keyword><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>04</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>05</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>5</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>6</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>5</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32425222</ArticleId><ArticleId IdType="doi">10.1016/j.encep.2020.05.006</ArticleId><ArticleId IdType="pii">S0013-7006(20)30091-9</ArticleId><ArticleId IdType="pmc">PMC7229964</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Plaze, M" sort="Plaze, M" uniqKey="Plaze M" first="M" last="Plaze">M. Plaze</name></region><name sortKey="Attali, D" sort="Attali, D" uniqKey="Attali D" first="D" last="Attali">D. Attali</name><name sortKey="Blatzer, M" sort="Blatzer, M" uniqKey="Blatzer M" first="M" last="Blatzer">M. Blatzer</name><name sortKey="Cachia, A" sort="Cachia, A" uniqKey="Cachia A" first="A" last="Cachia">A. Cachia</name><name sortKey="Chretien, F" sort="Chretien, F" uniqKey="Chretien F" first="F" last="Chrétien">F. Chrétien</name><name sortKey="Gaillard, R" sort="Gaillard, R" uniqKey="Gaillard R" first="R" last="Gaillard">R. Gaillard</name><name sortKey="Petit, A C" sort="Petit, A C" uniqKey="Petit A" first="A-C" last="Petit">A-C Petit</name><name sortKey="Simon Loriere, E" sort="Simon Loriere, E" uniqKey="Simon Loriere E" first="E" last="Simon-Loriere">E. Simon-Loriere</name><name sortKey="Vinckier, F" sort="Vinckier, F" uniqKey="Vinckier F" first="F" last="Vinckier">F. Vinckier</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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