Enhanced virucidal activity of quaternary ammonium compound-thymol combinations: influence of mucin and mucoadhesive polymers.

The COVID-19 pandemic highlighted the potential of oral antiseptic agents to reduce viral transmission. Strategies that enhance and sustain antiviral activity in the oral cavity may further support control of respiratory viruses. In this study, we evaluated the virucidal activity of selected antiseptic agents against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), individually and in combination, under controlled in vitro conditions. Cetylpyridinium chloride (CPC), benzethonium chloride (BZT), thymol, and tannic acid were assessed using a quantitative suspension assay in the presence of mucin and representative mucoadhesive polymers. Dynamic light scattering and zeta potential analyses were performed to characterize interactions between active agents and mucin or polymers. CPC, BZT, and thymol exhibited dose-dependent viral inactivation. CPC reduced IAV and SARS-CoV-2 titres by approximately 4 log₁₀ at > 200 µg/mL and 25 µg/mL, respectively, while thymol achieved comparable reductions at 1000 µg/mL and 750 µg/mL. Tannic acid showed minimal virucidal activity. Notably, CPC-thymol and BZT-thymol combinations achieved > 4 log₁₀ reductions at substantially lower concentrations than individual agents, indicating enhanced virucidal activity and improved cytocompatibility. Mucin markedly attenuated the virucidal activity of CPC-thymol combinations; however, selected polymers partially preserved antiviral efficacy under mucin-rich conditions. Physicochemical analyses suggest that electrostatic, hydrophobic, and hydrogen-bonding interactions contribute to these effects. These findings demonstrate the enhanced antiviral activity of quaternary ammonium compound-thymol combinations and highlight the influence of mucosal components and macromolecules interactions in modulating oral antiseptic activity.