Pulmonary surfactant-derived antiviral actions at the respiratory surface

Lung surfactant (LS) is a membrane-based lipid-protein com-plex that lines the alveoli, reducing the surface tension at the air-liquid interface and thus minimizing the work of breathing. Besides this function, LS is also the first physical barrier be-tween the outside air and the systemic circulation, therefore playing a key role in the defense against harmful particles and microorganisms.Viral respiratory tract infections (RTIs), and especially acute lower RTIs, are one of the leading causes of morbidity and mortality worldwide. LS participates in the network of in-teractions between viruses and the immune system to prevent or lessen the effects of the infection, but it is also altered by these pathogens, which can potentially impair its function. The aim of this review is to provide an integrated multidisci-plinary overview toward understanding the interplay between respiratory viruses and LS and its health impact on the respi-ratory system. The review is centered on the antiviral mecha-nisms of both LS proteins and lipids, and their different interactions that lead to varying outcomes. Finally, a summary of the clinical application of surfactant in the scene of lung viral infection is disclosed, including state-of-the-art approaches of the therapeutic use of surfactant components.