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10.1016/j.ebiom.2020.103153

http://scihub22266oqcxt.onion/10.1016/j.ebiom.2020.103153
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33279857!7711201!33279857
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suck abstract from ncbi

pmid33279857      EBioMedicine 2021 ; 63 (?): 103153
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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 #MMPMID33279857
  • 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
  • EBioMedicine 2021[Jan]; 63 (?): 103153 PMID33279857show ga
  • 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 x 10(6) 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=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. INTERPRETATION: 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. FUNDING: This work was funded by Ena Respiratory, Melbourne, Australia.
  • |*Virus Shedding[MESH]
  • |Administration, Intranasal[MESH]
  • |Animals[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19/pathology[MESH]
  • |Disease Models, Animal[MESH]
  • |Female[MESH]
  • |Ferrets[MESH]
  • |Immunity, Innate[MESH]
  • |Lipopeptides/*administration & dosage/chemistry/pharmacology[MESH]
  • |Nasal Cavity/pathology/virology[MESH]
  • |Pharynx/pathology/virology[MESH]
  • |RNA, Viral/metabolism[MESH]
  • |Real-Time Polymerase Chain Reaction[MESH]
  • |Respiratory System/pathology/*virology[MESH]
  • |SARS-CoV-2/genetics/isolation & purification/*pathogenicity[MESH]
  • |Toll-Like Receptor 2/*agonists[MESH]
  • |Toll-Like Receptor 6/*agonists[MESH]


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