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Article

Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice

1
Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia
2
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Jeroen van Kampen, Pieter L. A. Fraaij and Oliver Schildgen
Viruses 2021, 13(8), 1656; https://doi.org/10.3390/v13081656
Received: 23 June 2021 / Revised: 6 August 2021 / Accepted: 18 August 2021 / Published: 20 August 2021
Strategies to combat COVID-19 require multiple ways to protect vulnerable people from infection. SARS-CoV-2 is an airborne pathogen and the nasal cavity is a primary target of infection. The K18-hACE2 mouse model was used to investigate the anti-SARS-CoV-2 efficacy of astodrimer sodium formulated in a mucoadhesive nasal spray. Animals received astodrimer sodium 1% nasal spray or PBS intranasally, or intranasally and intratracheally, for 7 days, and they were infected intranasally with SARS-CoV-2 after the first product administration on Day 0. Another group was infected intranasally with SARS-CoV-2 that had been pre-incubated with astodrimer sodium 1% nasal spray or PBS for 60 min before the neutralisation of test product activity. Astodrimer sodium 1% significantly reduced the viral genome copies (>99.9%) and the infectious virus (~95%) in the lung and trachea vs. PBS. The pre-incubation of SARS-CoV-2 with astodrimer sodium 1% resulted in a significant reduction in the viral genome copies (>99.9%) and the infectious virus (>99%) in the lung and trachea, and the infectious virus was not detected in the brain or liver. Astodrimer sodium 1% resulted in a significant reduction of viral genome copies in nasal secretions vs. PBS on Day 7 post-infection. A reduction in the viral shedding from the nasal cavity may result in lower virus transmission rates. Viraemia was low or undetectable in animals treated with astodrimer sodium 1% or infected with treated virus, correlating with the lack of detectable viral replication in the liver. Similarly, low virus replication in the nasal cavity after treatment with astodrimer sodium 1% potentially protected the brain from infection. Astodrimer sodium 1% significantly reduced the pro-inflammatory cytokines IL-6, IL-1α, IL-1β, TNFα and TGFβ and the chemokine MCP-1 in the serum, lung and trachea vs. PBS. Astodrimer sodium 1% nasal spray blocked or reduced SARS-CoV-2 replication and its sequelae in K18-hACE2 mice. These data indicate a potential role for the product in preventing SARS-CoV-2 infection or for reducing the severity of COVID-19. View Full-Text
Keywords: astodrimer; SPL7013; dendrimer; antiviral; SARS-CoV-2; COVID-19; nasal; animal model astodrimer; SPL7013; dendrimer; antiviral; SARS-CoV-2; COVID-19; nasal; animal model
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MDPI and ACS Style

Paull, J.R.A.; Luscombe, C.A.; Castellarnau, A.; Heery, G.P.; Bobardt, M.D.; Gallay, P.A. Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice. Viruses 2021, 13, 1656. https://doi.org/10.3390/v13081656

AMA Style

Paull JRA, Luscombe CA, Castellarnau A, Heery GP, Bobardt MD, Gallay PA. Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice. Viruses. 2021; 13(8):1656. https://doi.org/10.3390/v13081656

Chicago/Turabian Style

Paull, Jeremy R.A., Carolyn A. Luscombe, Alex Castellarnau, Graham P. Heery, Michael D. Bobardt, and Philippe A. Gallay 2021. "Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice" Viruses 13, no. 8: 1656. https://doi.org/10.3390/v13081656

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