학술논문
Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
Document Type
article
Author
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)
Subject
Language
English
ISSN
2352-3964
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=