Evidence map›Paper›PMID 33037151›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.

Suzanne J F Kaptein, Sofie Jacobs, Lana Langendries, Laura Seldeslachts, Sebastiaan Ter Horst, Laurens Liesenborghs, Bart Hens, Valentijn Vergote, Elisabeth Heylen, Karine Barthelemy and 25 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04981379 (Efficacy and Safety of the Use of Hydroxychloroquine, Favipiravir or Hydroxychloroquine + Favipiravir in Early SARS-CoV-2), which is not on this map. Cited by 166 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04981379 phase3completednot on this map

Efficacy and Safety of the Use of Hydroxychloroquine, Favipiravir or Hydroxychloroquine + Favipiravir in Early SARS-CoV-2 (COVID-19) Treatment

TypeinterventionalSponsorHealth Institutes of TurkeyRan2020 to 2021Enrolled1,120ConditionsCovid19ArmsHydroxychloroquine, Favipiravir, Favipiravir + Hydroxychloroquine, Placebo
3 · Its place in the literature

Who cites it

166 citing papers in PubMed, 2 syntheses or guidelines pooled it, 284 citations in OpenAlex.

  1. Pooled it
  2. Prophylaxis for COVID-19: a systematic review.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2021
    Pooled it
  3. Trial
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  7. Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2023
    Trial
  8. Trial
  9. Trial
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  11. Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2021
    Trial
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Andrographolide Inhibits Rabies Virus Replication.Transboundary and emerging diseases · 2026
    Article

106 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors at 5 institutions in 4 countries.

Suzanne J F KapteinLaboratory 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.ORCID 0000-0002-7935-0219
Sofie JacobsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-8657-6841
Lana LangendriesLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-6450-6324
Laura SeldeslachtsBiomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0002-9562-2923
Sebastiaan Ter HorstLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-7981-6376
Laurens LiesenborghsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-5616-8548
Bart HensDrug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.ORCID 0000-0002-4229-9843
Valentijn VergoteLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0002-4436-3212
Elisabeth HeylenLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0003-4359-7225
Karine BarthelemyUnité 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.
Elke MaasLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Carolien De KeyzerLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Lindsey BervoetsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Jasper RymenantsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0003-3838-310X
Tina Van BuytenLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Xin ZhangLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-8520-1060
Rana AbdelnabiLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-9771-7312
Juanita PangUCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.ORCID 0000-0002-4792-5903
Rachel WilliamsUCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.
Hendrik Jan ThibautLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0001-5785-8276
Kai DallmeierLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0002-8117-9166
Robbert BoudewijnsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0002-5984-7279
Jens WoutersMolecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Patrick AugustijnsDrug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.ORCID 0000-0003-2595-388X
Nick VerougstraeteDepartment of Laboratory Medicine, Ghent University Hospital, 9000 Ghent, Belgium.ORCID 0000-0002-8275-0125
Christopher CawthorneNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0002-5975-0354
Judith BreuerUCL Great Ormond Street Institute of Child Health, University College London, WC1N 1EH London, United Kingdom.ORCID 0000-0001-8246-0534
Caroline SolasAssistance 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.ORCID 0000-0002-0943-9648
Birgit WeynandTranslational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0003-4246-6303
Pieter AnnaertDrug Delivery & Disposition, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.ORCID 0000-0003-3525-7351
Isabel SprietPharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.
Greetje Vande VeldeBiomedical MRI and Molecular Small Animal Imaging Centre, Department of Imaging and Pathology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.ORCID 0000-0002-5633-3993
Johan NeytsLaboratory 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.ORCID 0000-0002-0033-7514
Joana Rocha-PereiraLaboratory 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.ORCID 0000-0001-8299-3787
Leen DelangLaboratory 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.ORCID 0000-0002-8874-675X
Rega Institute for Medical Research · BEKU Leuven · BEUniversity College London · GBInserm · FRGhent University Hospital · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AmidesAnimalsAntiviral AgentsBetacoronavirusChlorocebus aethiopsCoronavirus InfectionsCOVID-19 Drug TreatmentCricetinaeDisease Models, AnimalDisease Transmission, InfectiousDose-Response Relationship, DrugDrug Evaluation, PreclinicalFemaleHydroxychloroquineLungPyrazinesAmidesAntiviral AgentsfavipiravirHydroxychloroquinePyrazinesantiviral therapyfavipiravirhydroxychloroquinepreclinical modelSARS-CoV-2

Identifiers

PMID33037151
PMCPMC7604414
OpenAlexW3092285496

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.