Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.
Identifieur interne : 001294 ( Main/Exploration ); précédent : 001293; suivant : 001295Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.
Auteurs : Suzanne J F. Kaptein [Belgique] ; Sofie Jacobs [Belgique] ; Lana Langendries [Belgique] ; Laura Seldeslachts [Belgique] ; Sebastiaan Ter Horst [Belgique] ; Laurens Liesenborghs [Belgique] ; Bart Hens [Belgique] ; Valentijn Vergote [Belgique] ; Elisabeth Heylen [Belgique] ; Karine Barthelemy [France] ; Elke Maas [Belgique] ; Carolien De Keyzer [Belgique] ; Lindsey Bervoets [Belgique] ; Jasper Rymenants [Belgique] ; Tina Van Buyten [Belgique] ; Xin Zhang [Belgique] ; Rana Abdelnabi [Belgique] ; Juanita Pang [Royaume-Uni] ; Rachel Williams [Royaume-Uni] ; Hendrik Jan Thibaut [Belgique] ; Kai Dallmeier [Belgique] ; Robbert Boudewijns [Belgique] ; Jens Wouters [Belgique] ; Patrick Augustijns [Belgique] ; Nick Verougstraete [Belgique] ; Christopher Cawthorne [Belgique] ; Judith Breuer [Royaume-Uni] ; Caroline Solas [France] ; Birgit Weynand [Belgique] ; Pieter Annaert [Belgique] ; Isabel Spriet [Belgique] ; Greetje Vande Velde [Belgique] ; Johan Neyts [Belgique, États-Unis] ; Joana Rocha-Pereira [Belgique] ; Leen Delang [Belgique]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2020.
Descripteurs français
- KwdFr :
- Amides (pharmacocinétique), Amides (usage thérapeutique), Animaux (MeSH), Antiviraux (usage thérapeutique), Betacoronavirus (effets des médicaments et des substances chimiques), Cellules Vero (MeSH), Charge virale (effets des médicaments et des substances chimiques), Cricetinae (MeSH), Femelle (MeSH), Hydroxychloroquine (pharmacocinétique), Hydroxychloroquine (usage thérapeutique), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Modèles animaux de maladie humaine (MeSH), Poumon (anatomopathologie), Poumon (effets des médicaments et des substances chimiques), Poumon (virologie), Pyrazines (pharmacocinétique), Pyrazines (usage thérapeutique), Relation dose-effet des médicaments (MeSH), Résultat thérapeutique (MeSH), Transmission de maladie infectieuse (prévention et contrôle), Évaluation préclinique de médicament (MeSH).
- MESH :
- anatomopathologie : Poumon.
- effets des médicaments et des substances chimiques : Betacoronavirus, Charge virale, Poumon.
- pharmacocinétique : Amides, Hydroxychloroquine, Pyrazines.
- prévention et contrôle : Transmission de maladie infectieuse.
- traitement médicamenteux : Infections à coronavirus.
- usage thérapeutique : Amides, Antiviraux, Hydroxychloroquine, Pyrazines.
- virologie : Infections à coronavirus, Poumon.
- Animaux, Cellules Vero, Cricetinae, Femelle, Modèles animaux de maladie humaine, Relation dose-effet des médicaments, Résultat thérapeutique, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Amides (pharmacokinetics), Amides (therapeutic use), Animals (MeSH), Antiviral Agents (therapeutic use), Betacoronavirus (drug effects), COVID-19 (drug therapy), Chlorocebus aethiops (MeSH), Coronavirus Infections (drug therapy), Coronavirus Infections (virology), Cricetinae (MeSH), Disease Models, Animal (MeSH), Disease Transmission, Infectious (prevention & control), Dose-Response Relationship, Drug (MeSH), Drug Evaluation, Preclinical (MeSH), Female (MeSH), Hydroxychloroquine (pharmacokinetics), Hydroxychloroquine (therapeutic use), Lung (drug effects), Lung (pathology), Lung (virology), Pyrazines (pharmacokinetics), Pyrazines (therapeutic use), SARS-CoV-2 (MeSH), Treatment Outcome (MeSH), Vero Cells (MeSH), Viral Load (drug effects).
- MESH :
- chemical , pharmacokinetics : Amides, Hydroxychloroquine, Pyrazines.
- chemical , therapeutic use : Amides, Antiviral Agents, Hydroxychloroquine, Pyrazines.
- drug effects : Betacoronavirus, Lung, Viral Load.
- drug therapy : COVID-19, Coronavirus Infections.
- pathology : Lung.
- prevention & control : Disease Transmission, Infectious.
- virology : Coronavirus Infections, Lung.
- Animals, Chlorocebus aethiops, Cricetinae, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Female, SARS-CoV-2, Treatment Outcome, Vero Cells.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.
DOI: 10.1073/pnas.2014441117
PubMed: 33037151
PubMed Central: PMC7604414
Affiliations:
- Belgique, France, Royaume-Uni, États-Unis
- Angleterre, Grand Londres, Maryland, Provence-Alpes-Côte d'Azur, Province de Flandre-Orientale, Province du Brabant flamand, Région flamande
- Gand, Londres, Louvain, Marseille
- Katholieke Universiteit Leuven, University College de Londres
Links toward previous steps (curation, corpus...)
Le document en format XML
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type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Barthelemy, Karine" sort="Barthelemy, Karine" uniqKey="Barthelemy K" first="Karine" last="Barthelemy">Karine Barthelemy</name><affiliation wicri:level="3"><nlm:affiliation>Unité des Virus Emergents, Aix Marseille University, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, 13005 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Emergents, Aix Marseille University, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, 13005 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Maas, Elke" sort="Maas, Elke" uniqKey="Maas E" first="Elke" last="Maas">Elke Maas</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="De Keyzer, Carolien" sort="De Keyzer, Carolien" uniqKey="De Keyzer C" first="Carolien" last="De Keyzer">Carolien De Keyzer</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Bervoets, Lindsey" sort="Bervoets, Lindsey" uniqKey="Bervoets L" first="Lindsey" last="Bervoets">Lindsey Bervoets</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Rymenants, Jasper" sort="Rymenants, Jasper" uniqKey="Rymenants J" first="Jasper" last="Rymenants">Jasper Rymenants</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Van Buyten, Tina" sort="Van Buyten, Tina" uniqKey="Van Buyten T" first="Tina" last="Van Buyten">Tina Van Buyten</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Zhang, Xin" sort="Zhang, Xin" uniqKey="Zhang X" first="Xin" last="Zhang">Xin Zhang</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Abdelnabi, Rana" sort="Abdelnabi, Rana" uniqKey="Abdelnabi R" first="Rana" last="Abdelnabi">Rana Abdelnabi</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Pang, Juanita" sort="Pang, Juanita" uniqKey="Pang J" first="Juanita" last="Pang">Juanita Pang</name><affiliation wicri:level="4"><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Williams, Rachel" sort="Williams, Rachel" uniqKey="Williams R" first="Rachel" last="Williams">Rachel Williams</name><affiliation wicri:level="4"><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Thibaut, Hendrik Jan" sort="Thibaut, Hendrik Jan" uniqKey="Thibaut H" first="Hendrik Jan" last="Thibaut">Hendrik Jan Thibaut</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Dallmeier, Kai" sort="Dallmeier, Kai" uniqKey="Dallmeier K" first="Kai" last="Dallmeier">Kai Dallmeier</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Boudewijns, Robbert" sort="Boudewijns, Robbert" uniqKey="Boudewijns R" first="Robbert" last="Boudewijns">Robbert Boudewijns</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Wouters, Jens" sort="Wouters, Jens" uniqKey="Wouters J" first="Jens" last="Wouters">Jens Wouters</name><affiliation wicri:level="4"><nlm:affiliation>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Augustijns, Patrick" sort="Augustijns, Patrick" uniqKey="Augustijns P" first="Patrick" last="Augustijns">Patrick Augustijns</name><affiliation wicri:level="4"><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName><orgName type="university">Katholieke Universiteit Leuven</orgName></affiliation></author><author><name sortKey="Verougstraete, Nick" sort="Verougstraete, Nick" uniqKey="Verougstraete N" first="Nick" last="Verougstraete">Nick Verougstraete</name><affiliation wicri:level="3"><nlm:affiliation>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent</wicri:regionArea><placeName><region type="province" nuts="2">Province de Flandre-Orientale</region><settlement type="city">Gand</settlement></placeName></affiliation></author><author><name sortKey="Cawthorne, Christopher" sort="Cawthorne, Christopher" uniqKey="Cawthorne C" first="Christopher" last="Cawthorne">Christopher Cawthorne</name><affiliation wicri:level="4"><nlm:affiliation>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Breuer, Judith" sort="Breuer, Judith" uniqKey="Breuer J" first="Judith" last="Breuer">Judith Breuer</name><affiliation wicri:level="4"><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Unité des Virus Emergents, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, Laboratoire de Pharmacocinétique et Toxicologie, 13005 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Unité des Virus Emergents, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, Laboratoire de Pharmacocinétique et Toxicologie, 13005 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Weynand, Birgit" sort="Weynand, Birgit" uniqKey="Weynand B" first="Birgit" last="Weynand">Birgit Weynand</name><affiliation wicri:level="4"><nlm:affiliation>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Annaert, Pieter" sort="Annaert, Pieter" uniqKey="Annaert P" first="Pieter" last="Annaert">Pieter Annaert</name><affiliation wicri:level="4"><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName><orgName type="university">Katholieke Universiteit Leuven</orgName></affiliation></author><author><name sortKey="Spriet, Isabel" sort="Spriet, Isabel" uniqKey="Spriet I" first="Isabel" last="Spriet">Isabel Spriet</name><affiliation wicri:level="3"><nlm:affiliation>Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Pharmacy Department, University Hospitals Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Vande Velde, Greetje" sort="Vande Velde, Greetje" uniqKey="Vande Velde G" first="Greetje" last="Vande Velde">Greetje Vande Velde</name><affiliation wicri:level="4"><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Global Virus Network, Baltimore, MD 21201.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Global Virus Network, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Rocha Pereira, Joana" sort="Rocha Pereira, Joana" uniqKey="Rocha Pereira J" first="Joana" last="Rocha-Pereira">Joana Rocha-Pereira</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Delang, Leen" sort="Delang, Leen" uniqKey="Delang L" first="Leen" last="Delang">Leen Delang</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33037151</idno><idno type="pmid">33037151</idno><idno type="doi">10.1073/pnas.2014441117</idno><idno type="pmc">PMC7604414</idno><idno type="wicri:Area/Main/Corpus">000A67</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000A67</idno><idno type="wicri:Area/Main/Curation">000A67</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000A67</idno><idno type="wicri:Area/Main/Exploration">000A67</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.</title><author><name sortKey="Kaptein, Suzanne J F" sort="Kaptein, Suzanne J F" uniqKey="Kaptein S" first="Suzanne J F" last="Kaptein">Suzanne J F. Kaptein</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Jacobs, Sofie" sort="Jacobs, Sofie" uniqKey="Jacobs S" first="Sofie" last="Jacobs">Sofie Jacobs</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Langendries, Lana" sort="Langendries, Lana" uniqKey="Langendries L" first="Lana" last="Langendries">Lana Langendries</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Seldeslachts, Laura" sort="Seldeslachts, Laura" uniqKey="Seldeslachts L" first="Laura" last="Seldeslachts">Laura Seldeslachts</name><affiliation wicri:level="4"><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Ter Horst, Sebastiaan" sort="Ter Horst, Sebastiaan" uniqKey="Ter Horst S" first="Sebastiaan" last="Ter Horst">Sebastiaan Ter Horst</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Liesenborghs, Laurens" sort="Liesenborghs, Laurens" uniqKey="Liesenborghs L" first="Laurens" last="Liesenborghs">Laurens Liesenborghs</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Hens, Bart" sort="Hens, Bart" uniqKey="Hens B" first="Bart" last="Hens">Bart Hens</name><affiliation wicri:level="4"><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName><orgName type="university">Katholieke Universiteit Leuven</orgName></affiliation></author><author><name sortKey="Vergote, Valentijn" sort="Vergote, Valentijn" uniqKey="Vergote V" first="Valentijn" last="Vergote">Valentijn Vergote</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Heylen, Elisabeth" sort="Heylen, Elisabeth" uniqKey="Heylen E" first="Elisabeth" last="Heylen">Elisabeth Heylen</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Barthelemy, Karine" sort="Barthelemy, Karine" uniqKey="Barthelemy K" first="Karine" last="Barthelemy">Karine Barthelemy</name><affiliation wicri:level="3"><nlm:affiliation>Unité des Virus Emergents, Aix Marseille University, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, 13005 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité des Virus Emergents, Aix Marseille University, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, 13005 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Maas, Elke" sort="Maas, Elke" uniqKey="Maas E" first="Elke" last="Maas">Elke Maas</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="De Keyzer, Carolien" sort="De Keyzer, Carolien" uniqKey="De Keyzer C" first="Carolien" last="De Keyzer">Carolien De Keyzer</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Bervoets, Lindsey" sort="Bervoets, Lindsey" uniqKey="Bervoets L" first="Lindsey" last="Bervoets">Lindsey Bervoets</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Rymenants, Jasper" sort="Rymenants, Jasper" uniqKey="Rymenants J" first="Jasper" last="Rymenants">Jasper Rymenants</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Van Buyten, Tina" sort="Van Buyten, Tina" uniqKey="Van Buyten T" first="Tina" last="Van Buyten">Tina Van Buyten</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Zhang, Xin" sort="Zhang, Xin" uniqKey="Zhang X" first="Xin" last="Zhang">Xin Zhang</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Abdelnabi, Rana" sort="Abdelnabi, Rana" uniqKey="Abdelnabi R" first="Rana" last="Abdelnabi">Rana Abdelnabi</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Pang, Juanita" sort="Pang, Juanita" uniqKey="Pang J" first="Juanita" last="Pang">Juanita Pang</name><affiliation wicri:level="4"><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Williams, Rachel" sort="Williams, Rachel" uniqKey="Williams R" first="Rachel" last="Williams">Rachel Williams</name><affiliation wicri:level="4"><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Thibaut, Hendrik Jan" sort="Thibaut, Hendrik Jan" uniqKey="Thibaut H" first="Hendrik Jan" last="Thibaut">Hendrik Jan Thibaut</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Dallmeier, Kai" sort="Dallmeier, Kai" uniqKey="Dallmeier K" first="Kai" last="Dallmeier">Kai Dallmeier</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Boudewijns, Robbert" sort="Boudewijns, Robbert" uniqKey="Boudewijns R" first="Robbert" last="Boudewijns">Robbert Boudewijns</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Wouters, Jens" sort="Wouters, Jens" uniqKey="Wouters J" first="Jens" last="Wouters">Jens Wouters</name><affiliation wicri:level="4"><nlm:affiliation>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Augustijns, Patrick" sort="Augustijns, Patrick" uniqKey="Augustijns P" first="Patrick" last="Augustijns">Patrick Augustijns</name><affiliation wicri:level="4"><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName><orgName type="university">Katholieke Universiteit Leuven</orgName></affiliation></author><author><name sortKey="Verougstraete, Nick" sort="Verougstraete, Nick" uniqKey="Verougstraete N" first="Nick" last="Verougstraete">Nick Verougstraete</name><affiliation wicri:level="3"><nlm:affiliation>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent</wicri:regionArea><placeName><region type="province" nuts="2">Province de Flandre-Orientale</region><settlement type="city">Gand</settlement></placeName></affiliation></author><author><name sortKey="Cawthorne, Christopher" sort="Cawthorne, Christopher" uniqKey="Cawthorne C" first="Christopher" last="Cawthorne">Christopher Cawthorne</name><affiliation wicri:level="4"><nlm:affiliation>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Breuer, Judith" sort="Breuer, Judith" uniqKey="Breuer J" first="Judith" last="Breuer">Judith Breuer</name><affiliation wicri:level="4"><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Unité des Virus Emergents, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, Laboratoire de Pharmacocinétique et Toxicologie, 13005 Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Unité des Virus Emergents, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, Laboratoire de Pharmacocinétique et Toxicologie, 13005 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Weynand, Birgit" sort="Weynand, Birgit" uniqKey="Weynand B" first="Birgit" last="Weynand">Birgit Weynand</name><affiliation wicri:level="4"><nlm:affiliation>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Annaert, Pieter" sort="Annaert, Pieter" uniqKey="Annaert P" first="Pieter" last="Annaert">Pieter Annaert</name><affiliation wicri:level="4"><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName><orgName type="university">Katholieke Universiteit Leuven</orgName></affiliation></author><author><name sortKey="Spriet, Isabel" sort="Spriet, Isabel" uniqKey="Spriet I" first="Isabel" last="Spriet">Isabel Spriet</name><affiliation wicri:level="3"><nlm:affiliation>Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Pharmacy Department, University Hospitals Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven</wicri:regionArea><placeName><region type="province" nuts="2">Province du Brabant flamand</region><settlement type="city">Louvain</settlement></placeName></affiliation></author><author><name sortKey="Vande Velde, Greetje" sort="Vande Velde, Greetje" uniqKey="Vande Velde G" first="Greetje" last="Vande Velde">Greetje Vande Velde</name><affiliation wicri:level="4"><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Global Virus Network, Baltimore, MD 21201.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Global Virus Network, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Rocha Pereira, Joana" sort="Rocha Pereira, Joana" uniqKey="Rocha Pereira J" first="Joana" last="Rocha-Pereira">Joana Rocha-Pereira</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author><author><name sortKey="Delang, Leen" sort="Delang, Leen" uniqKey="Delang L" first="Leen" last="Delang">Leen Delang</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</nlm:affiliation><country wicri:rule="url">Belgique</country><wicri:regionArea>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven</wicri:regionArea><orgName type="university">Katholieke Universiteit Leuven</orgName><placeName><settlement type="city">Louvain</settlement><region>Région flamande</region><region type="district" nuts="2">Province du Brabant flamand</region></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amides (pharmacokinetics)</term><term>Amides (therapeutic use)</term><term>Animals (MeSH)</term><term>Antiviral Agents (therapeutic use)</term><term>Betacoronavirus (drug effects)</term><term>COVID-19 (drug therapy)</term><term>Chlorocebus aethiops (MeSH)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (virology)</term><term>Cricetinae (MeSH)</term><term>Disease Models, Animal (MeSH)</term><term>Disease Transmission, Infectious (prevention & control)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Drug Evaluation, Preclinical (MeSH)</term><term>Female (MeSH)</term><term>Hydroxychloroquine (pharmacokinetics)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Lung (drug effects)</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Pyrazines (pharmacokinetics)</term><term>Pyrazines (therapeutic use)</term><term>SARS-CoV-2 (MeSH)</term><term>Treatment Outcome (MeSH)</term><term>Vero Cells (MeSH)</term><term>Viral Load (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amides (pharmacocinétique)</term><term>Amides (usage thérapeutique)</term><term>Animaux (MeSH)</term><term>Antiviraux (usage thérapeutique)</term><term>Betacoronavirus (effets des médicaments et des substances chimiques)</term><term>Cellules Vero (MeSH)</term><term>Charge virale (effets des médicaments et des substances chimiques)</term><term>Cricetinae (MeSH)</term><term>Femelle (MeSH)</term><term>Hydroxychloroquine (pharmacocinétique)</term><term>Hydroxychloroquine (usage thérapeutique)</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Infections à coronavirus (virologie)</term><term>Modèles animaux de maladie humaine (MeSH)</term><term>Poumon (anatomopathologie)</term><term>Poumon (effets des médicaments et des substances chimiques)</term><term>Poumon (virologie)</term><term>Pyrazines (pharmacocinétique)</term><term>Pyrazines (usage thérapeutique)</term><term>Relation dose-effet des médicaments (MeSH)</term><term>Résultat thérapeutique (MeSH)</term><term>Transmission de maladie infectieuse (prévention et contrôle)</term><term>Évaluation préclinique de médicament (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Amides</term><term>Hydroxychloroquine</term><term>Pyrazines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Amides</term><term>Antiviral Agents</term><term>Hydroxychloroquine</term><term>Pyrazines</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Betacoronavirus</term><term>Lung</term><term>Viral Load</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Betacoronavirus</term><term>Charge virale</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Amides</term><term>Hydroxychloroquine</term><term>Pyrazines</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Disease Transmission, Infectious</term></keywords><keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Transmission de maladie infectieuse</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Amides</term><term>Antiviraux</term><term>Hydroxychloroquine</term><term>Pyrazines</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Cricetinae</term><term>Disease Models, Animal</term><term>Dose-Response Relationship, Drug</term><term>Drug Evaluation, Preclinical</term><term>Female</term><term>SARS-CoV-2</term><term>Treatment Outcome</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Cricetinae</term><term>Femelle</term><term>Modèles animaux de maladie humaine</term><term>Relation dose-effet des médicaments</term><term>Résultat thérapeutique</term><term>Évaluation préclinique de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33037151</PMID><DateCompleted><Year>2020</Year><Month>11</Month><Day>09</Day></DateCompleted><DateRevised><Year>2021</Year><Month>03</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1091-6490</ISSN><JournalIssue CitedMedium="Internet"><Volume>117</Volume><Issue>43</Issue><PubDate><Year>2020</Year><Month>10</Month><Day>27</Day></PubDate></JournalIssue><Title>Proceedings of the National Academy of Sciences of the United States of America</Title><ISOAbbreviation>Proc Natl Acad Sci U S A</ISOAbbreviation></Journal><ArticleTitle>Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.</ArticleTitle><Pagination><MedlinePgn>26955-26965</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1073/pnas.2014441117</ELocationID><Abstract><AbstractText>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.</AbstractText><CopyrightInformation>Copyright © 2020 the Author(s). Published by PNAS.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kaptein</LastName><ForeName>Suzanne J F</ForeName><Initials>SJF</Initials><Identifier Source="ORCID">0000-0002-7935-0219</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jacobs</LastName><ForeName>Sofie</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-8657-6841</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Langendries</LastName><ForeName>Lana</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0001-6450-6324</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seldeslachts</LastName><ForeName>Laura</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-9562-2923</Identifier><AffiliationInfo><Affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ter Horst</LastName><ForeName>Sebastiaan</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-7981-6376</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liesenborghs</LastName><ForeName>Laurens</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0001-5616-8548</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hens</LastName><ForeName>Bart</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0002-4229-9843</Identifier><AffiliationInfo><Affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vergote</LastName><ForeName>Valentijn</ForeName><Initials>V</Initials><Identifier Source="ORCID">0000-0002-4436-3212</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heylen</LastName><ForeName>Elisabeth</ForeName><Initials>E</Initials><Identifier Source="ORCID">0000-0003-4359-7225</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barthelemy</LastName><ForeName>Karine</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Unité des Virus Emergents, Aix Marseille University, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, 13005 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maas</LastName><ForeName>Elke</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>De Keyzer</LastName><ForeName>Carolien</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bervoets</LastName><ForeName>Lindsey</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rymenants</LastName><ForeName>Jasper</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-3838-310X</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Buyten</LastName><ForeName>Tina</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xin</ForeName><Initials>X</Initials><Identifier Source="ORCID">0000-0001-8520-1060</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abdelnabi</LastName><ForeName>Rana</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0001-9771-7312</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pang</LastName><ForeName>Juanita</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-4792-5903</Identifier><AffiliationInfo><Affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Williams</LastName><ForeName>Rachel</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thibaut</LastName><ForeName>Hendrik Jan</ForeName><Initials>HJ</Initials><Identifier Source="ORCID">0000-0001-5785-8276</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dallmeier</LastName><ForeName>Kai</ForeName><Initials>K</Initials><Identifier Source="ORCID">0000-0002-8117-9166</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boudewijns</LastName><ForeName>Robbert</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0002-5984-7279</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wouters</LastName><ForeName>Jens</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Augustijns</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0003-2595-388X</Identifier><AffiliationInfo><Affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Verougstraete</LastName><ForeName>Nick</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0002-8275-0125</Identifier><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cawthorne</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0002-5975-0354</Identifier><AffiliationInfo><Affiliation>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Breuer</LastName><ForeName>Judith</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0001-8246-0534</Identifier><AffiliationInfo><Affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Solas</LastName><ForeName>Caroline</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0002-0943-9648</Identifier><AffiliationInfo><Affiliation>Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Unité des Virus Emergents, Institut de Recherche pour le Développement (IRD) 190, Institut National de la Santé et de la Recherche Médicale (INSERM) 1207, Laboratoire de Pharmacocinétique et Toxicologie, 13005 Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weynand</LastName><ForeName>Birgit</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0003-4246-6303</Identifier><AffiliationInfo><Affiliation>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Annaert</LastName><ForeName>Pieter</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0003-3525-7351</Identifier><AffiliationInfo><Affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spriet</LastName><ForeName>Isabel</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vande Velde</LastName><ForeName>Greetje</ForeName><Initials>G</Initials><Identifier Source="ORCID">0000-0002-5633-3993</Identifier><AffiliationInfo><Affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neyts</LastName><ForeName>Johan</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-0033-7514</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Global Virus Network, Baltimore, MD 21201.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rocha-Pereira</LastName><ForeName>Joana</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0001-8299-3787</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Delang</LastName><ForeName>Leen</ForeName><Initials>L</Initials><Identifier Source="ORCID">0000-0002-8874-675X</Identifier><AffiliationInfo><Affiliation>Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; suzanne.kaptein@kuleuven.be johan.neyts@kuleuven.be joana.rochapereira@kuleuven.be leen.delang@kuleuven.be.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>10</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Proc Natl Acad Sci U S A</MedlineTA><NlmUniqueID>7505876</NlmUniqueID><ISSNLinking>0027-8424</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000577">Amides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011719">Pyrazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EW5GL2X7E0</RegistryNumber><NameOfSubstance UI="C462182">favipiravir</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000577" MajorTopicYN="N">Amides</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006224" MajorTopicYN="N">Cricetinae</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018562" MajorTopicYN="N">Disease Transmission, Infectious</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004353" MajorTopicYN="N">Drug Evaluation, Preclinical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011719" MajorTopicYN="N">Pyrazines</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019562" MajorTopicYN="N">Viral Load</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword><Keyword MajorTopicYN="Y">antiviral therapy</Keyword><Keyword MajorTopicYN="Y">favipiravir</Keyword><Keyword MajorTopicYN="Y">hydroxychloroquine</Keyword><Keyword MajorTopicYN="Y">preclinical model</Keyword></KeywordList><CoiStatement>The authors declare no competing interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>10</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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