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Significance Medical visits and missed days of school and work caused by rhinoviruses cost tens of billions of US dollars annually. Currently, there are no antivirals against rhinoviruses, and the available treatments only treat the symptoms. Here, we present the molecular structure of human rhinovirus 14 in complex with its cellular receptor intercellular adhesion molecule 1. The binding of the virus to its receptor initiates the infection. Knowledge of the structure of the human rhinovirus 14–intercellular adhesion molecule 1 interface and mechanism of interaction provides the basis for the design of compounds that may block the binding of rhinoviruses to receptors and thus prevent infection.

ICAM-1 induced rearrangements of capsid and genome prime rhinovirus 14 for activation and uncoating