Mechanisms for Physicochemical Interaction between Mucus and Respiratory Viruses

Viral infections of the respiratory tract, including those caused by respiratory syncytial virus, influenza, and coronaviruses, constitute a significant global public health burden. Central to the pathogenesis of these infections are the interactions between viruses and host mucosal barriers, particularly the complex glycoproteins known as mucins that are the primary constituents of mucus. Mucins function not only as physical barriers but also as immune modulators, with their glycan chains playing critical roles in viral recognition and binding processes. These viral-mucin interactions determine host specificity, influence transmission dynamics, and regulate immune responses. Conversely, viruses can alter mucus composition and compromise mucociliary clearance mechanisms. This review first examines the structural and functional properties of mucins, followed by a comprehensive analysis of the complex interactions between respiratory viral surface proteins and mucins, including virus-induced perturbations to airway mucus secretion. We summarize current knowledge of viral-mucin interactions to provide insights into the potential development of mucin-mimetic polymers for targeted viral engagement, with applications ranging from viral detection to infection inhibition. Additionally, we discuss biophysical methodologies for investigating interactions between viruses and glycans.