Flaviviruses are small spherical virus particles covered by a dense icosahedral array of envelope (E) proteins that mediate virus attachment to cells and the fusion of viral and cellular membranes. Our understanding of the mechanism by which flavivirus E proteins orchestrate entry into cells has been advanced by studies of E structure and arrangement on the virion at different steps of the virus entry/membrane fusion process. When combined with an increasingly clear (albeit still incomplete) view of the cell biology of virus entry, these advances suggest new antiviral strategies. Indeed, inhibitors that target cellular and viral processes involved in entry show promise as powerful tools to study this critical step of the viral lifecycle, and with luck, may ultimately lead to therapeutic advances.
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