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HAdV infections typically cause mild symptoms; however, individuals such as children, those with underlying conditions, and those with compromised immune systems can develop severe disseminated disease. Our results demonstrate that ivermectin, an FDA-approved antiparasitic agent, is effective at inhibiting replication of several HAdV types\n            <jats:italic>in vitro<\/jats:italic>\n            . This is in agreement with the growing body of literature suggesting ivermectin has broad antiviral activity. This study expands our mechanistic knowledge of ivermectin by showing that ivermectin targets the ability of importin-\u03b1 (Imp-\u03b1) to recognize nuclear localization sequences, without effecting the Imp-\u03b1\/\u03b21 interaction. 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