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Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

Authors :
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 Thomas
Nadina I. Wand
Paul Yeates
Christophe Demaison
Weiguang Zeng
Ian Holmes
David C. Jackson
Nathan W. Bartlett
Francesca Mercuri
Miles W. Carroll
Source :
EBioMedicine, Vol 63, Iss , Pp 103153- (2021)
Publication Year :
2021
Publisher :
Elsevier, 2021.

Abstract

Background: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, 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. Methods: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). Findings: 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. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=

Details

Language :
English
ISSN :
23523964
Volume :
63
Issue :
103153-
Database :
Directory of Open Access Journals
Journal :
EBioMedicine
Publication Type :
Academic Journal
Accession number :
edsdoj.f31e56098d3d48869b5be4927c46a453
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ebiom.2020.103153