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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
- Source :
- EBioMedicine, EBioMedicine, Vol 63, Iss, Pp 103153-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 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=
- Subjects :
- 0301 basic medicine
viruses
Respiratory System
lcsh:Medicine
medicine.disease_cause
0302 clinical medicine
Medicine
Respiratory system
Coronavirus
Virus quantification
lcsh:R5-920
TLR-2
General Medicine
Viral Load
Virus Shedding
medicine.anatomical_structure
030220 oncology & carcinogenesis
RNA, Viral
Female
Nasal Cavity
lcsh:Medicine (General)
Viral load
Research Paper
Real-Time Polymerase Chain Reaction
Virus
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Lipopeptides
Animals
Ferret
Viral shedding
Administration, Intranasal
Lung
business.industry
SARS-CoV-2
lcsh:R
Ferrets
COVID-19
Virology
Immunity, Innate
Toll-Like Receptor 2
COVID-19 Drug Treatment
INNA-051
Disease Models, Animal
030104 developmental biology
Toll-Like Receptor 6
Pharynx
business
Respiratory tract
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....b21cacb67acae468a1e1f7b7e9cd3eae
- Full Text :
- https://doi.org/10.1016/j.ebiom.2020.103153