Influenza inhibiting compositions and methods

An isolated peptide consisting of 8 to 40 consecutive amino acid residues of a portion of a selected wild-type influenza hemagglutinin 2 protein or a variant thereof, the portion of the selected hemagglutinin 2 protein comprising the fusion initiation region (FIR) of the protein and up to five amino acid residues on the amino-terminal and carboxy-terminal sides of the FIR and including at least the sequence YNAELL (SEQ ID NO:

• 1) or a variant thereof that differs from SEQ ID NO:
• 1 by one or more amino acid substitutions selected from the group consisting of Y1S, Y1T, Y1W, Y1A, N2Q, A3L, A3I, A3V, E4D, E4K, E4R, E4H, 15I, 15V, 15A, 16I, 16V, and 16A;
• the amino acid sequence of the FIR comprising that portion of the selected wild-type hemagglutinin 2 (HA2) protein beginning at about residue 77 in the N-helix of the protein, and ending at a residue in the range of residue 110 to residue 119 of the selected wild-type hemagglutinin 2 protein, the carboxy-terminus of the FIR being the residue immediately preceding the first residue beginning a region of increasing Wimley-White interfacial hydrophobicity beyond residue 104 of the wild-type sequence;
• the variant differing from the selected wild-type protein by one or more amino acid substitutions in the amino acid sequence of the portion of the selected wild-type protein;
• the substitutions being selected from corresponding amino acid residues of other wild-type influenza HA2 proteins, and preferably being selected so as to maintain a Wimley-White interfacial hydropathy profile for the variant having local maxima and local minima within about 5 amino acid residues of the local maxima and local minima of the Wimley-White interfacial hydropathy profile of the corresponding region of at least one wild-type HA2 protein.