Epithelial cell damage affects not only the skin, which covers the external surface of the human body, but also the non-keratinized epithelia, the mucosa, that lines the surfaces of internal organs, including the nasopharynx and lungs. This mucosa is characterized by a moist surface formed by the mucus overlying the epithelial cells. In the respiratory tract in particular, mucosa cells are constantly exposed to large amounts of environmental pathogens and stressors, including bacteria and viruses inhaled as aerosols. Therefore, mucins, a group of glycoproteins that constitute a major component of the mucus, play an important role in the innate immune defense provided by the protective mucus shield. This barrier function of the mucus can be disrupted by a number of agents, such as fine dust (particulate matter). Recent results have shown that inorganic polyphosphate (polyP), which can be administered, for example, in the form of a nasopharyngeal spray, offers a promising way to strengthen or repair impaired mucus function. This chapter describes the structure and formation of the mucus and its mucin building blocks, as well as the mode of action of polyP and drug-loaded polyP nanoparticles in restoring the mucus barrier, particularly with regard to their protective function against coronavirus infection.