PT  - JOURNAL ARTICLE
AU  - Suzanne JF Kaptein
AU  - Sofie Jacobs
AU  - Lana Langendries
AU  - Laura Seldeslachts
AU  - Sebastiaan ter Horst
AU  - Laurens Liesenborghs
AU  - Bart Hens
AU  - Valentijn Vergote
AU  - Elisabeth Heylen
AU  - Elke Maas
AU  - Carolien De Keyzer
AU  - Lindsey Bervoets
AU  - Jasper Rymenants
AU  - Tina Van Buyten
AU  - Hendrik Jan Thibaut
AU  - Kai Dallmeier
AU  - Robbert Boudewijns
AU  - Jens Wouters
AU  - Patrick Augustijns
AU  - Nick Verougstraete
AU  - Christopher Cawthorne
AU  - Birgit Weynand
AU  - Pieter Annaert
AU  - Isabel Spriet
AU  - Greetje Vande Velde
AU  - Johan Neyts
AU  - Joana Rocha-Pereira
AU  - Leen Delang
TI  - Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine
AID  - 10.1101/2020.06.19.159053
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.19.159053
4099  - http://biorxiv.org/content/early/2020/06/19/2020.06.19.159053.short
4100  - http://biorxiv.org/content/early/2020/06/19/2020.06.19.159053.full
AB  - 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 was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinical in vivo evidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studying in vivo efficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reported in vivo data in macaques and ferrets) provide no scientific basis for further use of the drug in humans.Competing Interest StatementThe authors have declared no competing interest.