Table 2_Reframing clathrin-mediated viral entry: evidence standards, context dependence and host-directed vulnerabilities.docx

This structured narrative review synthesizes evidence from database searches and citation tracking performed up to 18 June 2026. Clathrin-mediated endocytosis (CME) can internalize virus-receptor complexes and deliver them to endosomal compartments that support penetration, fusion, capsid remodeling, uncoating or genome release.

However, CME should be interpreted as a series of experimentally separable checkpoints rather than as a single pathway label. Viral use of CME varies with strain, receptor and cofactor availability, host-cell type, membrane composition, protease environment, inoculum size and synchronization conditions. Strict CME-dependent entry is assigned only when direct perturbation of core or proximal CME machinery, supported by rescue or an orthogonal approach, converges with stage-resolved evidence of productive virion progression through clathrin/AP-2-positive coated pits or vesicles and an early functional entry readout in a defined virus-receptor-cell context.