A Skin Organoid-Based Infection Platform Identifies an Inhibitor Specific for Hand, Foot, and Mouth Disease

The study utilized human induced pluripotent stem cell-derived skin organoids (hiPSC-SOs) to investigate Enterovirus 71 (EV-A71) infection, a major cause of hand, foot, and mouth disease (HFMD) in children. It identified fibroblasts and epidermal cells as primary targets, with autophagy and abnormal proliferation of epidermal progenitor cells being key mechanisms. The FDA-approved inhibitor NSC167409 was found to effectively inhibit EV-A71 replication by suppressing virus-induced autophagy and inflammation, suggesting its potential as a therapeutic agent. The study also linked EV-A71 infection to skin aging and tumorigenesis and identified hair follicle stem cells as target cells, indicating a potential impact on hair growth. The research highlights the utility of skin organoid models in antiviral drug development, despite limitations such as the absence of blood vessels and immune cells.