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

Publication date: Jun 18, 2026

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 ug/mL and 25 ug/mL, respectively, while thymol achieved comparable reductions at 1000 ug/mL and 750 ug/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.

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Concepts Keywords
1000g Animals
Antiseptic Anti-Infective Agents, Local
Cetylpyridinium Anti-Infective Agents, Local
Coronavirus Antiviral Agents
Improved Antiviral Agents
Benzethonium
Benzethonium
Benzethonium chloride
Betacoronavirus
Cetylpyridinium
Cetylpyridinium
Cetylpyridinium chloride
COVID-19
Dogs
Humans
Influenza A
Influenza A virus
Mucins
Mucins
Polymers
Polymers
Quaternary Ammonium Compounds
Quaternary Ammonium Compounds
Respiratory viruses
SARS-CoV-2
SARS-CoV-2
Tannins
Tannins
Thymol
Thymol
Thymol
Virucidal activity

Semantics

Type Source Name
drug DRUGBANK Thymol
disease MESH COVID-19 pandemic
drug DRUGBANK Influenza A virus
disease MESH severe acute respiratory syndrome
drug DRUGBANK Cetylpyridinium
drug DRUGBANK Chloride ion
drug DRUGBANK Benzethonium
drug DRUGBANK Tannic acid
disease MESH cam
disease MESH influenza
drug DRUGBANK Chlorhexidine
drug DRUGBANK Povidone-iodine
drug DRUGBANK Hydrogen peroxide
disease MESH parainfluenza
drug DRUGBANK Benzydamine
drug DRUGBANK Phosphate ion
disease MESH dis
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Carboxymethylcellulose
drug DRUGBANK Polyvinyl alcohol
drug DRUGBANK Hydroxyethyl cellulose
drug DRUGBANK Water
disease MESH FBS
drug DRUGBANK Streptomycin
drug DRUGBANK Geneticin
drug DRUGBANK Trypsin
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH included
drug DRUGBANK Cysteamine
disease MESH PALS
drug DRUGBANK Trestolone
drug DRUGBANK Coenzyme M
pathway KEGG Influenza A

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