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

de Melo, G. D.; Lazarini, F.; Larrous, F.; Feige, L.; Kergoat, L.; Marchio, A.; Pineau, P.; Lecuit, M.; Lledo, P.-M.; Changeux, J.-P.; Bourhy, H.

doi:10.1101/2020.11.21.392639

bioRxiv · 10.1101/2020.11.21.392639

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

de Melo, G. D.·Lazarini, F.·Larrous, F.·Feige, L.·Kergoat, L.·Marchio, A.·Pineau, P.·Lecuit, M.·Lledo, P.-M.·Changeux, J.-P.·Bourhy, H.

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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 -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.

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de Melo, G. D., Lazarini, F., Larrous, F., Feige, L., Kergoat, L., Marchio, A., Pineau, P., Lecuit, M., Lledo, P.-M., Changeux, J.-P., Bourhy, H.. 2020-11-22. Anti-COVID-19 efficacy of ivermectin in the golden hamster. https://doi.org/10.1101/2020.11.21.392639

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