Abstract: The present invention demonstrates that the M2-1 protein of respiratory syncytial virus has a conserved Cys3—His1 motif known to bind zinc ions in other proteins and that mutations of the predicted zinc coordinating residues in the Cys3—His1 motif affect the transcriptional antitermination activity of M2-1, its ability to interact with nucleocapsid protein, and the phosphorylation state of M2-1. This invention clearly demonstrates the requirement for conservation of the Cys3—His1 motif in order to maintain the functional integrity of the M2-1 protein. Therefore, the present invention provides for methods of designing and screening compounds for antiviral activity towards respiratory syncytial virus based upon the loss of function of the M2-1 protein.

Abstract: The present invention demonstrates that the M2-1 protein of respiratory syncytial virus has a conserved Cys3-His1 motif known to bind zinc ions in other proteins and that mutations of the predicted zinc coordinating residues in the Cys3-His1 motif affect the transcriptional antitermination activity of M2-1, its ability to interact with nucleocapsid protein, and the phosphorylation state of M2-1. This invention clearly demonstrates the requirement for conservation of the Cys3-His1 motif in order to maintain the functional integrity of the M2-1 protein. Therefore, the present invention provides for methods of designing and screening compounds for antiviral activity towards respiratory syncytial virus based upon the loss of function of the M2-1 protein.