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Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

By Pamela C. Proud, Daphne Tsitoura, Robert J Watson, Brendon Y. Chua, Marilyn J Aram, Kevin R Bewley, Breeze E Cavell, Rebecca Cobb, Stuart Dowall, Susan A Fotheringham, Catherine M K Ho, Vanessa Lucas, Didier Ngabo, Emma Rayner, Kathryn A Ryan, Gillian S Slack, Stephen A. Thomas, Nadina I Wand, Paul Yeates, Christophe Demaison, David C. Jackson, Nathan W Bartlett, Francesca Mercuri, Miles W Carroll

Posted 25 Sep 2020
bioRxiv DOI: 10.1101/2020.09.25.309914 (published DOI: 10.1016/j.ebiom.2020.103153)

Respiratory viruses such as coronaviruses represent major ongoing global threats, causing epidemics and pandemics with huge economic burden. Rapid spread of virus through populations poses an enormous challenge for outbreak control. Like all respiratory viruses, the most recent novel human coronavirus SARS-CoV-2, initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

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