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

DOI record: { "DOI": "10.3390/v13081656", "ISSN": [ "1999-4915" ], "URL": "http://dx.doi.org/10.3390/v13081656", "abstract": "<jats:p>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 (&gt;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 (&gt;99.9%) and the infectious virus (&gt;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.</jats:p>", "alternative-id": [ "v13081656" ], "author": [ { "ORCID": "http://orcid.org/0000-0002-9981-421X", "affiliation": [ { "name": "Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia" } ], "authenticated-orcid": false, "family": "Paull", "given": "Jeremy R. A.", "sequence": "first" }, { "affiliation": [ { "name": "Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia" } ], "family": "Luscombe", "given": "Carolyn A.", "sequence": "additional" }, { "affiliation": [ { "name": "Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia" } ], "family": "Castellarnau", "given": "Alex", "sequence": "additional" }, { "affiliation": [ { "name": "Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia" } ], "family": "Heery", "given": "Graham P.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USA" } ], "family": "Bobardt", "given": "Michael D.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USA" } ], "family": "Gallay", "given": "Philippe A.", "sequence": "additional" } ], "container-title": "Viruses", "container-title-short": "Viruses", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 8, 23 ] ], "date-time": "2021-08-23T03:00:09Z", "timestamp": 1629687609000 }, "deposited": { "date-parts": [ [ 2024, 7, 17 ] ], "date-time": "2024-07-17T16:42:17Z", "timestamp": 1721234537000 }, "funder": [ { "award": [ "BTBR300093" ], "name": "Australian Medical Research Future Fund (MRFF) Biomedical Translation Bridge (BTB) Program" } ], "indexed": { "date-parts": [ [ 2024, 9, 6 ] ], "date-time": "2024-09-06T10:14:46Z", "timestamp": 1725617686809 }, "is-referenced-by-count": 16, "issue": "8", "issued": { "date-parts": [ [ 2021, 8, 20 ] ] }, "journal-issue": { "issue": "8", "published-online": { "date-parts": [ [ 2021, 8 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 8, 20 ] ], "date-time": "2021-08-20T00:00:00Z", "timestamp": 1629417600000 } } ], "link": [ { "URL": "https://www.mdpi.com/1999-4915/13/8/1656/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "1656", "prefix": "10.3390", "published": { "date-parts": [ [ 2021, 8, 20 ] ] }, "published-online": { "date-parts": [ [ 2021, 8, 20 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1016/S0140-6736(20)32656-8", "article-title": "6-month consequences of COVID-19 in patients discharged from hospital: A cohort study", "author": "Huang", "doi-asserted-by": "crossref", "first-page": "220", "journal-title": "Lancet", "key": "ref_1", "volume": "397", "year": "2021" }, { "DOI": "10.1016/j.antiviral.2021.105089", "article-title": "Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro", "author": "Paull", "doi-asserted-by": "crossref", "first-page": "105089", "journal-title": "Antivir. 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