Nasal application of a chitosan-sialic acid formulation mitigates the risk of viral respiratory infections in mouse model

Respiratory virus infections pose a significant threat to the public health. Although vaccination and antiviral therapy are effective in preventing and treating these infections, they are challenged by issues of efficacy, safety, and compliance. Mucosal barrier is a natural defense system developed through evolution, with mucus playing a key role in blocking pathogen invasions. Maintaining an intact mucus layer of respiratory tract is an effective and convenient measure complementary to vaccination. Chitosan is an alkaline polysaccharide derived from natural sources that is biocompatible and safe for human. Its positively charged amino groups and ability to polymerize in acidic conditions give it adhesive properties for mucosal coating. Sialic acids are commonly exploited by various viruses as binding sites for entering host cells and can act as decoy receptors when attached to the chitosan polymer. Here, we present a chitosan-sialic acid complex (CS) that blocks influenza and respiratory syncytial viruses from attaching to and entering susceptible cells in culture. Applying this complex to the nasal cavities of mice mitigates the risk of viral infection and prevents pulmonary inflammation. These results demonstrate the potential of CS as a mucus analogue and a universal prophylactic agent for preventing a range of upper respiratory infections.