Cathepsins in cellular entry of human pathogenic viruses

In the life cycle of a virus, host cell entry represents the first step that a virus needs to undertake to gain access to the cell interior for replication. Once a virus attaches itself to its target cell receptor, it activates endogenous cellular responses and exploits host cell factors for its internalization, fusion, and genome release. Among the host factors that critically contribute to the viral entry processes are cathepsins, which are the most abundant endo/lysosomal proteases with diverse physiological functions. This review summarizes previous findings on how different cathepsins contribute to the host cell entry of human pathogenic viruses, focusing on their specific roles in the entry processes of both enveloped and non-enveloped RNA viruses. A comprehensive knowledge of the functions of different cathepsins in viral entry will provide valuable insights into the molecular mechanisms underlying viral infections and can be useful in the development of new antiviral strategies.