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Abstract
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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the airborne viral pathogen that causes the pandemic coronavirus disease of 2019 (COVID-19)
The current study extends the established antiviral and virucidal activity of astodrimer sodium against SARS-CoV-2 in vitro to evaluate, in a recognised in vivo challenge model of infection, the ability of the compound in a nasal spray formulation to protect against and reduce the severity of SARS-CoV-2 infection via the upper respiratory tract of K18-human ACE2 (hACE2) mice
Animals in Groups 1.2 and 2.2 that were treated with astodrimer sodium 1% nasal spray formulation had undetectable levels of viraemia on Day 4 post-infection, and while viraemia was detectable on Day 7 post-infection, the level was very low (~0.03 log10 viral genome copies/mL) (Figure 1)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the airborne viral pathogen that causes the pandemic coronavirus disease of 2019 (COVID-19). The COVID19 pandemic has resulted in significant worldwide deaths, and the search for strategies to reduce the incidence and clinical severity of the disease continues. The most common symptoms of long-COVID are fatigue, shortness of breath, tightness of the chest, racing heart, difficulty concentrating and brain fog, loss of smell and taste, loss of appetite, hair loss, difficulty sleeping, anxiety and depression [1]. Many of those who suffer from long-COVID had mild initial symptoms and were not hospitalised. There is an urgent need to develop strategies to prevent SARS-CoV-2 infection to eliminate the potential adverse events that infection can cause
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