Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.
Identifieur interne : 000A67 ( Main/Corpus ); précédent : 000A66; suivant : 000A68Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.
Auteurs : Suzanne J F. Kaptein ; Sofie Jacobs ; Lana Langendries ; Laura Seldeslachts ; Sebastiaan Ter Horst ; Laurens Liesenborghs ; Bart Hens ; Valentijn Vergote ; Elisabeth Heylen ; Karine Barthelemy ; Elke Maas ; Carolien De Keyzer ; Lindsey Bervoets ; Jasper Rymenants ; Tina Van Buyten ; Xin Zhang ; Rana Abdelnabi ; Juanita Pang ; Rachel Williams ; Hendrik Jan Thibaut ; Kai Dallmeier ; Robbert Boudewijns ; Jens Wouters ; Patrick Augustijns ; Nick Verougstraete ; Christopher Cawthorne ; Judith Breuer ; Caroline Solas ; Birgit Weynand ; Pieter Annaert ; Isabel Spriet ; Greetje Vande Velde ; Johan Neyts ; Joana Rocha-Pereira ; Leen DelangSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2020.
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
Links to Exploration step
pubmed:33037151Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><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><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></affiliation></author><author><name sortKey="Jacobs, Sofie" sort="Jacobs, Sofie" uniqKey="Jacobs S" first="Sofie" last="Jacobs">Sofie Jacobs</name><affiliation><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></affiliation></author><author><name sortKey="Langendries, Lana" sort="Langendries, Lana" uniqKey="Langendries L" first="Lana" last="Langendries">Lana Langendries</name><affiliation><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></affiliation></author><author><name sortKey="Seldeslachts, Laura" sort="Seldeslachts, Laura" uniqKey="Seldeslachts L" first="Laura" last="Seldeslachts">Laura Seldeslachts</name><affiliation><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Liesenborghs, Laurens" sort="Liesenborghs, Laurens" uniqKey="Liesenborghs L" first="Laurens" last="Liesenborghs">Laurens Liesenborghs</name><affiliation><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></affiliation></author><author><name sortKey="Hens, Bart" sort="Hens, Bart" uniqKey="Hens B" first="Bart" last="Hens">Bart Hens</name><affiliation><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Vergote, Valentijn" sort="Vergote, Valentijn" uniqKey="Vergote V" first="Valentijn" last="Vergote">Valentijn Vergote</name><affiliation><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></affiliation></author><author><name sortKey="Heylen, Elisabeth" sort="Heylen, Elisabeth" uniqKey="Heylen E" first="Elisabeth" last="Heylen">Elisabeth Heylen</name><affiliation><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></affiliation></author><author><name sortKey="Barthelemy, Karine" sort="Barthelemy, Karine" uniqKey="Barthelemy K" first="Karine" last="Barthelemy">Karine Barthelemy</name><affiliation><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></affiliation></author><author><name sortKey="Maas, Elke" sort="Maas, Elke" uniqKey="Maas E" first="Elke" last="Maas">Elke Maas</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Bervoets, Lindsey" sort="Bervoets, Lindsey" uniqKey="Bervoets L" first="Lindsey" last="Bervoets">Lindsey Bervoets</name><affiliation><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></affiliation></author><author><name sortKey="Rymenants, Jasper" sort="Rymenants, Jasper" uniqKey="Rymenants J" first="Jasper" last="Rymenants">Jasper Rymenants</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Zhang, Xin" sort="Zhang, Xin" uniqKey="Zhang X" first="Xin" last="Zhang">Xin Zhang</name><affiliation><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></affiliation></author><author><name sortKey="Abdelnabi, Rana" sort="Abdelnabi, Rana" uniqKey="Abdelnabi R" first="Rana" last="Abdelnabi">Rana Abdelnabi</name><affiliation><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></affiliation></author><author><name sortKey="Pang, Juanita" sort="Pang, Juanita" uniqKey="Pang J" first="Juanita" last="Pang">Juanita Pang</name><affiliation><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Williams, Rachel" sort="Williams, Rachel" uniqKey="Williams R" first="Rachel" last="Williams">Rachel Williams</name><affiliation><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Dallmeier, Kai" sort="Dallmeier, Kai" uniqKey="Dallmeier K" first="Kai" last="Dallmeier">Kai Dallmeier</name><affiliation><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></affiliation></author><author><name sortKey="Boudewijns, Robbert" sort="Boudewijns, Robbert" uniqKey="Boudewijns R" first="Robbert" last="Boudewijns">Robbert Boudewijns</name><affiliation><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></affiliation></author><author><name sortKey="Wouters, Jens" sort="Wouters, Jens" uniqKey="Wouters J" first="Jens" last="Wouters">Jens Wouters</name><affiliation><nlm:affiliation>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Augustijns, Patrick" sort="Augustijns, Patrick" uniqKey="Augustijns P" first="Patrick" last="Augustijns">Patrick Augustijns</name><affiliation><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Verougstraete, Nick" sort="Verougstraete, Nick" uniqKey="Verougstraete N" first="Nick" last="Verougstraete">Nick Verougstraete</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Cawthorne, Christopher" sort="Cawthorne, Christopher" uniqKey="Cawthorne C" first="Christopher" last="Cawthorne">Christopher Cawthorne</name><affiliation><nlm:affiliation>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Breuer, Judith" sort="Breuer, Judith" uniqKey="Breuer J" first="Judith" last="Breuer">Judith Breuer</name><affiliation><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><affiliation><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></affiliation></author><author><name sortKey="Weynand, Birgit" sort="Weynand, Birgit" uniqKey="Weynand B" first="Birgit" last="Weynand">Birgit Weynand</name><affiliation><nlm:affiliation>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Annaert, Pieter" sort="Annaert, Pieter" uniqKey="Annaert P" first="Pieter" last="Annaert">Pieter Annaert</name><affiliation><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Spriet, Isabel" sort="Spriet, Isabel" uniqKey="Spriet I" first="Isabel" last="Spriet">Isabel Spriet</name><affiliation><nlm:affiliation>Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven, Belgium.</nlm:affiliation></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><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name><affiliation><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></affiliation><affiliation><nlm:affiliation>Global Virus Network, Baltimore, MD 21201.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Delang, Leen" sort="Delang, Leen" uniqKey="Delang L" first="Leen" last="Delang">Leen Delang</name><affiliation><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></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></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><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></affiliation></author><author><name sortKey="Jacobs, Sofie" sort="Jacobs, Sofie" uniqKey="Jacobs S" first="Sofie" last="Jacobs">Sofie Jacobs</name><affiliation><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></affiliation></author><author><name sortKey="Langendries, Lana" sort="Langendries, Lana" uniqKey="Langendries L" first="Lana" last="Langendries">Lana Langendries</name><affiliation><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></affiliation></author><author><name sortKey="Seldeslachts, Laura" sort="Seldeslachts, Laura" uniqKey="Seldeslachts L" first="Laura" last="Seldeslachts">Laura Seldeslachts</name><affiliation><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Liesenborghs, Laurens" sort="Liesenborghs, Laurens" uniqKey="Liesenborghs L" first="Laurens" last="Liesenborghs">Laurens Liesenborghs</name><affiliation><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></affiliation></author><author><name sortKey="Hens, Bart" sort="Hens, Bart" uniqKey="Hens B" first="Bart" last="Hens">Bart Hens</name><affiliation><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Vergote, Valentijn" sort="Vergote, Valentijn" uniqKey="Vergote V" first="Valentijn" last="Vergote">Valentijn Vergote</name><affiliation><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></affiliation></author><author><name sortKey="Heylen, Elisabeth" sort="Heylen, Elisabeth" uniqKey="Heylen E" first="Elisabeth" last="Heylen">Elisabeth Heylen</name><affiliation><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></affiliation></author><author><name sortKey="Barthelemy, Karine" sort="Barthelemy, Karine" uniqKey="Barthelemy K" first="Karine" last="Barthelemy">Karine Barthelemy</name><affiliation><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></affiliation></author><author><name sortKey="Maas, Elke" sort="Maas, Elke" uniqKey="Maas E" first="Elke" last="Maas">Elke Maas</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Bervoets, Lindsey" sort="Bervoets, Lindsey" uniqKey="Bervoets L" first="Lindsey" last="Bervoets">Lindsey Bervoets</name><affiliation><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></affiliation></author><author><name sortKey="Rymenants, Jasper" sort="Rymenants, Jasper" uniqKey="Rymenants J" first="Jasper" last="Rymenants">Jasper Rymenants</name><affiliation><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></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><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></affiliation></author><author><name sortKey="Zhang, Xin" sort="Zhang, Xin" uniqKey="Zhang X" first="Xin" last="Zhang">Xin Zhang</name><affiliation><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></affiliation></author><author><name sortKey="Abdelnabi, Rana" sort="Abdelnabi, Rana" uniqKey="Abdelnabi R" first="Rana" last="Abdelnabi">Rana Abdelnabi</name><affiliation><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></affiliation></author><author><name sortKey="Pang, Juanita" sort="Pang, Juanita" uniqKey="Pang J" first="Juanita" last="Pang">Juanita Pang</name><affiliation><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Williams, Rachel" sort="Williams, Rachel" uniqKey="Williams R" first="Rachel" last="Williams">Rachel Williams</name><affiliation><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Dallmeier, Kai" sort="Dallmeier, Kai" uniqKey="Dallmeier K" first="Kai" last="Dallmeier">Kai Dallmeier</name><affiliation><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></affiliation></author><author><name sortKey="Boudewijns, Robbert" sort="Boudewijns, Robbert" uniqKey="Boudewijns R" first="Robbert" last="Boudewijns">Robbert Boudewijns</name><affiliation><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></affiliation></author><author><name sortKey="Wouters, Jens" sort="Wouters, Jens" uniqKey="Wouters J" first="Jens" last="Wouters">Jens Wouters</name><affiliation><nlm:affiliation>Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Augustijns, Patrick" sort="Augustijns, Patrick" uniqKey="Augustijns P" first="Patrick" last="Augustijns">Patrick Augustijns</name><affiliation><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Verougstraete, Nick" sort="Verougstraete, Nick" uniqKey="Verougstraete N" first="Nick" last="Verougstraete">Nick Verougstraete</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Cawthorne, Christopher" sort="Cawthorne, Christopher" uniqKey="Cawthorne C" first="Christopher" last="Cawthorne">Christopher Cawthorne</name><affiliation><nlm:affiliation>Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Breuer, Judith" sort="Breuer, Judith" uniqKey="Breuer J" first="Judith" last="Breuer">Judith Breuer</name><affiliation><nlm:affiliation>UCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name><affiliation><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></affiliation></author><author><name sortKey="Weynand, Birgit" sort="Weynand, Birgit" uniqKey="Weynand B" first="Birgit" last="Weynand">Birgit Weynand</name><affiliation><nlm:affiliation>Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Annaert, Pieter" sort="Annaert, Pieter" uniqKey="Annaert P" first="Pieter" last="Annaert">Pieter Annaert</name><affiliation><nlm:affiliation>Drug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Spriet, Isabel" sort="Spriet, Isabel" uniqKey="Spriet I" first="Isabel" last="Spriet">Isabel Spriet</name><affiliation><nlm:affiliation>Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven-University of Leuven, 3000 Leuven, Belgium.</nlm:affiliation></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><nlm:affiliation>Biomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.</nlm:affiliation></affiliation></author><author><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name><affiliation><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></affiliation><affiliation><nlm:affiliation>Global Virus Network, Baltimore, MD 21201.</nlm:affiliation></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><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></affiliation></author><author><name sortKey="Delang, Leen" sort="Delang, Leen" uniqKey="Delang L" first="Leen" last="Delang">Leen Delang</name><affiliation><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></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="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="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="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Disease Transmission, Infectious</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></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 PubStatus="medline"><Year>2020</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>10</Month><Day>10</Day><Hour>5</Hour><Minute>29</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33037151</ArticleId><ArticleId IdType="pii">2014441117</ArticleId><ArticleId IdType="doi">10.1073/pnas.2014441117</ArticleId><ArticleId IdType="pmc">PMC7604414</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>N Engl J Med. 2020 Feb 20;382(8):727-733</Citation><ArticleIdList><ArticleId IdType="pubmed">31978945</ArticleId></ArticleIdList></Reference><Reference><Citation>Bioinformatics. 2016 Jan 15;32(2):292-4</Citation><ArticleIdList><ArticleId IdType="pubmed">26428292</ArticleId></ArticleIdList></Reference><Reference><Citation>Philos Trans R Soc Lond B Biol Sci. 2013 Feb 04;368(1614):20120205</Citation><ArticleIdList><ArticleId IdType="pubmed">23382427</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2020 Jul;583(7818):834-838</Citation><ArticleIdList><ArticleId IdType="pubmed">32408338</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 May 29;368(6494):1016-1020</Citation><ArticleIdList><ArticleId IdType="pubmed">32269068</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84</Citation><ArticleIdList><ArticleId IdType="pubmed">24841269</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 2004 Oct 8;323(1):264-8</Citation><ArticleIdList><ArticleId IdType="pubmed">15351731</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Infect Dis. 2020 Oct 23;71(7):e191-e194</Citation><ArticleIdList><ArticleId IdType="pubmed">32124919</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2020 Jun 11;181(6):1436-1441</Citation><ArticleIdList><ArticleId IdType="pubmed">32531248</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Negl Trop Dis. 2017 Feb 23;11(2):e0005389</Citation><ArticleIdList><ArticleId IdType="pubmed">28231247</ArticleId></ArticleIdList></Reference><Reference><Citation>Antiviral Res. 2018 May;153:85-94</Citation><ArticleIdList><ArticleId IdType="pubmed">29524445</ArticleId></ArticleIdList></Reference><Reference><Citation>Antiviral Res. 2020 Jun;178:104786</Citation><ArticleIdList><ArticleId IdType="pubmed">32251767</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2020 Jun 23;64(7):</Citation><ArticleIdList><ArticleId IdType="pubmed">32366720</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2019 Nov 26;9(1):17598</Citation><ArticleIdList><ArticleId IdType="pubmed">31772203</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2020 Jul 9;15(7):e0235458</Citation><ArticleIdList><ArticleId IdType="pubmed">32645044</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Res. 2020 Mar;30(3):269-271</Citation><ArticleIdList><ArticleId IdType="pubmed">32020029</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Pharmacol Ther. 2020 Aug;108(2):242-247</Citation><ArticleIdList><ArticleId IdType="pubmed">32246834</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Infect Dis. 2020 Jul 28;71(15):732-739</Citation><ArticleIdList><ArticleId IdType="pubmed">32150618</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur Heart J Acute Cardiovasc Care. 2020 Apr;9(3):209-214</Citation><ArticleIdList><ArticleId IdType="pubmed">32363880</ArticleId></ArticleIdList></Reference><Reference><Citation>Euro Surveill. 2020 Mar;25(9):</Citation><ArticleIdList><ArticleId IdType="pubmed">32156327</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2016 Dec 27;61(1):</Citation><ArticleIdList><ArticleId IdType="pubmed">27736754</ArticleId></ArticleIdList></Reference><Reference><Citation>Br J Clin Pharmacol. 1988 Sep;26(3):303-13</Citation><ArticleIdList><ArticleId IdType="pubmed">3179169</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Transl Sci. 2020 Sep;13(5):880-885</Citation><ArticleIdList><ArticleId IdType="pubmed">32475019</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2009 Jan;53(1):202-9</Citation><ArticleIdList><ArticleId IdType="pubmed">18955536</ArticleId></ArticleIdList></Reference><Reference><Citation>mBio. 2020 May 22;11(3):</Citation><ArticleIdList><ArticleId IdType="pubmed">32444382</ArticleId></ArticleIdList></Reference><Reference><Citation>Br J Pharmacol. 2020 Nov;177(21):4995-4996</Citation><ArticleIdList><ArticleId IdType="pubmed">32424836</ArticleId></ArticleIdList></Reference><Reference><Citation>Chirality. 1995;7(8):598-604</Citation><ArticleIdList><ArticleId IdType="pubmed">8593253</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Infect Dis. 2020 Dec 3;71(9):2428-2446</Citation><ArticleIdList><ArticleId IdType="pubmed">32215622</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 Aug 6;383(6):517-525</Citation><ArticleIdList><ArticleId IdType="pubmed">32492293</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Discov. 2020 Mar 18;6:16</Citation><ArticleIdList><ArticleId IdType="pubmed">32194981</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Pharmacol Ther. 2020 Aug;108(2):188</Citation><ArticleIdList><ArticleId IdType="pubmed">32350860</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2018 Nov 29;379(22):2173-2176</Citation><ArticleIdList><ArticleId IdType="pubmed">30485769</ArticleId></ArticleIdList></Reference><Reference><Citation>Antiviral Res. 2014 Apr;104:84-92</Citation><ArticleIdList><ArticleId IdType="pubmed">24486952</ArticleId></ArticleIdList></Reference><Reference><Citation>Dis Model Mech. 2016 Jan;9(1):91-8</Citation><ArticleIdList><ArticleId IdType="pubmed">26563390</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virus Erad. 2020 Apr 30;6(2):45-51</Citation><ArticleIdList><ArticleId IdType="pubmed">32405421</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Negl Trop Dis. 2013 Dec 26;7(12):e2614</Citation><ArticleIdList><ArticleId IdType="pubmed">24386500</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Pharmacol Ther. 2020 Aug;108(2):253-263</Citation><ArticleIdList><ArticleId IdType="pubmed">32285930</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2018 May 15;8(1):7604</Citation><ArticleIdList><ArticleId IdType="pubmed">29765101</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Host Microbe. 2020 May 13;27(5):704-709.e2</Citation><ArticleIdList><ArticleId IdType="pubmed">32259477</ArticleId></ArticleIdList></Reference><Reference><Citation>Lab Invest. 2016 Jun;96(6):692-704</Citation><ArticleIdList><ArticleId IdType="pubmed">27019389</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2020 May 29;368(6494):1012-1015</Citation><ArticleIdList><ArticleId IdType="pubmed">32303590</ArticleId></ArticleIdList></Reference><Reference><Citation>Br J Pharmacol. 2020 Nov;177(21):4851-4865</Citation><ArticleIdList><ArticleId IdType="pubmed">32462701</ArticleId></ArticleIdList></Reference><Reference><Citation>Pharmacol Res. 2020 Aug;158:104904</Citation><ArticleIdList><ArticleId IdType="pubmed">32430286</ArticleId></ArticleIdList></Reference><Reference><Citation>Genome Res. 2012 Mar;22(3):568-76</Citation><ArticleIdList><ArticleId IdType="pubmed">22300766</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2020 Sep;585(7824):268-272</Citation><ArticleIdList><ArticleId IdType="pubmed">32396922</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Immunol. 2020 Jun;20(6):363-374</Citation><ArticleIdList><ArticleId IdType="pubmed">32346093</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2020 Aug 4;10(1):13093</Citation><ArticleIdList><ArticleId IdType="pubmed">32753646</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A67 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 000A67 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= CovidChloroV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= pubmed:33037151
|texte= Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Corpus/RBID.i -Sk "pubmed:33037151" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a CovidChloroV1
| This area was generated with Dilib version V0.6.38. |  |