Abstract: The present invention relates to methods and compositions for inhibiting the entry of viruses, such as herpesviruses into a host cell. A conserved viral integrin-binding gB disintegrin-like domain has been identified that engages integrins and facilitates viral internalization into the host cell. Therefore, methods and compositions, such as antiviral agents encompassing the conserved gB disintegrin-like domain and antibodies thereto are described. These active agents interfere with the interaction between virions and cellular integrins, thereby inhibiting viral infection of a host cell.