Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice
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...
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/8/1656 |
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| author | Jeremy R. A. Paull Carolyn A. Luscombe Alex Castellarnau Graham P. Heery Michael D. Bobardt Philippe A. Gallay |
| author_facet | Jeremy R. A. Paull Carolyn A. Luscombe Alex Castellarnau Graham P. Heery Michael D. Bobardt Philippe A. Gallay |
| author_sort | Jeremy R. A. Paull |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:17:17Z |
| format | Article |
| id | doaj.art-1bc831e5c6b349fd9e86ebaee91475c4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T08:17:17Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1bc831e5c6b349fd9e86ebaee91475c42023-11-22T10:12:50ZengMDPI AGViruses1999-49152021-08-01138165610.3390/v13081656Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 MiceJeremy R. A. Paull0Carolyn A. Luscombe1Alex Castellarnau2Graham P. Heery3Michael D. Bobardt4Philippe A. Gallay5Starpharma Pty Ltd., Abbotsford, VIC 3067, AustraliaStarpharma Pty Ltd., Abbotsford, VIC 3067, AustraliaStarpharma Pty Ltd., Abbotsford, VIC 3067, AustraliaStarpharma Pty Ltd., Abbotsford, VIC 3067, AustraliaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USADepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USAStrategies 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.https://www.mdpi.com/1999-4915/13/8/1656astodrimerSPL7013dendrimerantiviralSARS-CoV-2COVID-19 |
| spellingShingle | Jeremy R. A. Paull Carolyn A. Luscombe Alex Castellarnau Graham P. Heery Michael D. Bobardt Philippe A. Gallay Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice Viruses astodrimer SPL7013 dendrimer antiviral SARS-CoV-2 COVID-19 |
| title | Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice |
| title_full | Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice |
| title_fullStr | Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice |
| title_full_unstemmed | Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice |
| title_short | Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice |
| title_sort | protective effects of astodrimer sodium 1 nasal spray formulation against sars cov 2 nasal challenge in k18 hace2 mice |
| topic | astodrimer SPL7013 dendrimer antiviral SARS-CoV-2 COVID-19 |
| url | https://www.mdpi.com/1999-4915/13/8/1656 |
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