The airway mucus barrier is both the first point of contact between respiratory viruses and the host and a frontline defense system that viruses must overcome prior to infection. Mucin glycoproteins within this barrier protect the underlying epithelium through trapping and clearance mechanisms and influence multiple aspects of viral pathogenesis including inflammation and transmission. Further, changes in mucin expression either associated with preexisting lung disease or induced during infection can affect disease severity. Research over the past century has aided our understanding of secreted and tethered mucin-mediated defenses and revealed insights into specific virus-mucin interactions and the effect of both physical virion attributes and viral glycoprotein function in facilitating mucus penetration. Here we discuss these advancements and highlight efforts to apply current knowledge to the development of mucin-inspired antiviral therapeutics. Still, given the diversity among respiratory viruses and complexity of mucin biology, open questions remain, indicating avenues for continued investigation.
Mathur et al. (2026) studied this question.