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Anti-COVID-19 efficacy of ivermectin in the golden hamster

View ORCID ProfileGuilherme Dias de Melo, Françoise Lazarini, Florence Larrous, Lena Feige, Lauriane Kergoat, Agnès Marchio, Pascal Pineau, View ORCID ProfileMarc Lecuit, Pierre-Marie Lledo, Jean-Pierre Changeux, Hervé Bourhy
doi: https://doi.org/10.1101/2020.11.21.392639
Guilherme Dias de Melo
1Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France
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  • ORCID record for Guilherme Dias de Melo
Françoise Lazarini
2Perception and Memory Unit, Institut Pasteur, CNRS UMR 3571, Paris, France
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Florence Larrous
1Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France
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Lena Feige
1Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France
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Lauriane Kergoat
1Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France
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Agnès Marchio
3Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France
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Pascal Pineau
3Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France
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Marc Lecuit
4Biology of Infection Unit, Institut Pasteur, Inserm U1117, Paris, France
5Université de Paris, Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, Institut Imagine, AP-HP, Paris, France
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Pierre-Marie Lledo
2Perception and Memory Unit, Institut Pasteur, CNRS UMR 3571, Paris, France
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Jean-Pierre Changeux
6Neuroscience Department, Institut Pasteur, Paris, France
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Hervé Bourhy
1Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France
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  • For correspondence: herve.bourhy@pasteur.fr
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Abstract

The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe1, and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune response2–5. Among therapeutic options6–8, the use of the anti-parasitic drug ivermectin (IVM), has been proposed, given its possible anti-SARS-CoV-2 activity9. Ivermectin is a positive allosteric modulator of the α-7 nicotinic acetylcholine receptor10, which has been suggested to represent a target for the control of Covid-19 infection11, with a potential immunomodulatory activity12. We assessed the effects of IVM in SARS-CoV-2-intranasally-inoculated golden Syrian hamsters. Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 22, 2020.
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Anti-COVID-19 efficacy of ivermectin in the golden hamster
Guilherme Dias de Melo, Françoise Lazarini, Florence Larrous, Lena Feige, Lauriane Kergoat, Agnès Marchio, Pascal Pineau, Marc Lecuit, Pierre-Marie Lledo, Jean-Pierre Changeux, Hervé Bourhy
bioRxiv 2020.11.21.392639; doi: https://doi.org/10.1101/2020.11.21.392639
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Anti-COVID-19 efficacy of ivermectin in the golden hamster
Guilherme Dias de Melo, Françoise Lazarini, Florence Larrous, Lena Feige, Lauriane Kergoat, Agnès Marchio, Pascal Pineau, Marc Lecuit, Pierre-Marie Lledo, Jean-Pierre Changeux, Hervé Bourhy
bioRxiv 2020.11.21.392639; doi: https://doi.org/10.1101/2020.11.21.392639

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