{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:19:14Z","timestamp":1784204354585,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Medical Research Future Fund (MRFF) Biomedical Translation Bridge (BTB) Program","award":["BTBR300093"],"award-info":[{"award-number":["BTBR300093"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"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-1\u03b1, IL-1\u03b2, TNF\u03b1 and TGF\u03b2 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>","DOI":"10.3390\/v13081656","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T23:00:09Z","timestamp":1629673209000},"page":"1656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9981-421X","authenticated-orcid":false,"given":"Jeremy R. A.","family":"Paull","sequence":"first","affiliation":[{"name":"Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Luscombe","sequence":"additional","affiliation":[{"name":"Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Castellarnau","sequence":"additional","affiliation":[{"name":"Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham P.","family":"Heery","sequence":"additional","affiliation":[{"name":"Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Bobardt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe A.","family":"Gallay","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0140-6736(20)32656-8","article-title":"6-month consequences of COVID-19 in patients discharged from hospital: A cohort study","volume":"397","author":"Huang","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105089","DOI":"10.1016\/j.antiviral.2021.105089","article-title":"Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro","volume":"191","author":"Paull","year":"2021","journal-title":"Antivir. 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