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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

Title: Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model
Authors: Proud, PC; Tsitoura, D; Watson, RJ; Chua, BY; Aram, MJ; Bewley, KR; Cavell, BE; Cobb, R; Dowall, S; Fotheringham, SA; Ho, CMK; Lucas, V; Ngabo, D; Rayner, E; Ryan, KA; Slack, GS; Thomas, S; Wand, NI; Yeates, P; Demaison, C; Zeng, W; Holmes, I; Jackson, DC; Bartlett, NW; Mercuri, F; Carroll, MW
Publisher Information: ELSEVIER
Publication Year: 2021
Collection: The University of Melbourne: Digital Repository
Description: 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=
Document Type: article in journal/newspaper
Language: English
ISSN: 2352-3964
Relation: https://hdl.handle.net/11343/272186
Availability: https://hdl.handle.net/11343/272186
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND
Accession Number: edsbas.563156D8
Database: BASE