Polypeptides for treating and/or limiting influenza infection

1. An isolated polypeptide comprising the polypeptide sequence according to general formula I

R1-R2-Phe-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17 (SEQ ID NO: 1), wherein

R1 is selected from the group consisting of Ser, Ala, Phe, His, Lys, Met, Asn, Gln, Thr, Val, Tyr, and Asp;

R2 can be any amino acid;

R3 is selected from the group consisting of Asp, Ala, Glu, Gly, Asn, Pro, Ser, and Tyr;

R4 is selected from the group consisting of Leu and Phe;

R5 can be any amino acid;

R6 is selected from the group consisting of Met, Phe, His, Ile, Leu, Gln, and Thr;

R7 is selected from the group consisting of Arg, Gly, Lys, Gln, and Thr; R8 is selected from the group consisting of Ile, Asn, Gln, Val, and Trp;

R9 is selected from the group consisting of Met, Gly, Ile, Lys, Leu, Asn, Arg, Ser, Thr, Val, His, and Tyr;

R10 is selected from the group consisting of Trp and Phe;

R11 is selected from the group consisting of Ile, Phe, Ser, Thr, and Val;

R12 is selected from the group consisting of Tyr, Cys, Asp, Phe, His, Asn, and Ser;

R13 is selected from the group consisting of Val, Ala, Phe, Ile, Leu, Asn, Gln, Thr, and Tyr;

R14 is selected from the group consisting of Phe, Glu, and Leu;

R15 is selected from the group consisting of Ala, Gly, Lys, Arg, and Ser; and

R16 is selected from the group consisting of Phe, Cys, His, Lys, Leu, Met, Asn, Gln, Arg, Thr, Val, Trp, and Tyr; wherein at least one of the following is true:

R3 is Asp, R6 is Met, R10 is Trp, or R14 is Phe.

2. The polypeptide of claim 1 , wherein general formula I comprises

R1-R2-Phe-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-X1-R17 (SEQ ID NO: 2), wherein

X1 is 4-8 amino acids in length, wherein each position can be any amino acid; and

R17 is Phe or Tyr.

3. The polypeptide according to claim 1 , wherein the polypeptide comprises a detectable tag.

4. A pharmaceutical composition, comprising one or more polypeptides according to claim 1 and a pharmaceutically acceptable carrier.

5. The polypeptide of claim 1 , wherein at least two of the following are true: R3 is Asp, R6 is Met, R10 is Trp, or R14 is Phe.

6. The polypeptide of claim 1 , wherein at least three of the following are true:

R3 is Asp, R6 is Met, R10 is Trp, or R14 is Phe.

7. The polypeptide of claim 1 , wherein R3 is Asp, R6 is Met, R10 is Trp, and R14 is Phe.

8. The polypeptide of claim 2 , wherein X1 comprises the amino acid sequence Z1-Arg-Z2-Ile-Pro (SEQ ID NO: 3), wherein Z1 is Lys or Asn, and Z2 is selected from the group consisting of Lys, Pro, and Thr.

9. The polypeptide of claim 1 , wherein general formula I is A1-R1-R2-Phe-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-X1-R17-B1 (SEQ ID NO: 4), wherein R1 through R17 and X1 are as defined above, wherein at least one of A1 and/or B1 are present,

wherein A1 comprises the amino acid sequence:

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYD(D/V/Y)EA(A/D)(A/K/R)VL(Q/K)AVY(E/A)T(N/D) (SEQ ID NO: 5); and

B1 comprises the amino acid sequence

(L/A/V)HA(Q/P)KLARRLLELK(Q/L)AASSPLP (SEQ ID NO: 6).

10. The polypeptide of claim 1 , selected from the group consisting of

(SEQ ID NO: 7)

SAFDLAMRIMWIYVFAF,

(SEQ ID NO: 8)

SAFDLAMRIMWIYVFAFKRPIPF,

(SEQ ID NO: 9)

DAFDLAMRIMWIYVFAFNRPIPF;

(SEQ ID NO: 10)

DAFDLAMRIMWIYVFAF;

(SEQ ID NO: 11)

SAFDLAMRIMWIYVFAFNRPIPF;

(SEQ ID NO: 7)

SAFDLAMRIMWIYVFAF;

(SEQ ID NO: 8)

SAFDLAMRIMWIYVFAFKRPIPF;

(SEQ ID NO: 15)

HAFDLAMRIHWIYVFAF;

(SEQ ID NO: 16)

HAFDLAMRIHWIYVFAFKRKIPF;

(SEQ ID NO: 17)

SAFDLAMRIIWIYVFAY;

(SEQ ID NO: 18)

SAFDLAMRIIWIYVFAYKRKIPF;

(SEQ ID NO: 19)

SAFDLAMRINWIYVFAF;

(SEQ ID NO: 20)

SAFDLAMRINWIYVFAFKRPIPF;

(SEQ ID NO: 21)

SAFDLAMRINWIYVFAF;

(SEQ ID NO: 22)

SAFDLAMRINWIYVFAFKRKIPF;

(SEQ ID NO: 23)

SAFDLAMTIHWIYNFAF;

(SEQ ID NO: 24)

SAFDLAMTIHWIYNFAFKRKIPF;

(SEQ ID NO: 25)

SAFDLAMRINWIYVFAF;

(SEQ ID NO: 26)

SAFDLAMRINWIYVFAFKRTIPF;

(SEQ ID NO: 27)

SAFDLAMRIHWIYIFAF;

(SEQ ID NO: 28)

SAFDLAMRIHWIYIFAFKRPIPF;

(SEQ ID NO: 29)

SAFDLAMRIHWIYNFAF;

(SEQ ID NO: 30)

SAFDLAMRIHWIYNFAFKRKIPF;

(SEQ ID NO: 31)

SAFDLAMRIHWIYNFAY;

(SEQ ID NO: 32)

SAFDLAMRIHWIYNFAYKRTIPF;

(SEQ ID NO: 33)

SAFDLAMRIHWIYNFAF;

(SEQ ID NO: 34)

SAFDLAMRIHWIYNFAFKRKIPF;

(SEQ ID NO: 35)

SAFDLAMRIHWIYIFAF;

(SEQ ID NO: 36)

SAFDLAMRIHWIYIFAFKRTIPF;

(SEQ ID NO: 37)

SAFDLAMRIHWIYNFAF;

(SEQ ID NO: 38)

SAFDLAMRIHWIYNFAFKRKIPF;

(SEQ ID NO: 39)

SAFDLAMKIHWIYNFAF;

(SEQ ID NO: 40)

SAFDLAMKIHWIYNFAFKRTIPF;

(SEQ ID NO: 41)

SAFDLAMKIHWIYIFAF;

(SEQ ID NO: 42)

SAFDLAMKIHWIYIFAFKRTIPF;

(SEQ ID NO: 44)

HAFDLAMRIMWIYVFAF;

(SEQ ID NO: 45)

SAFDLAMKIMWIYVFAF;

(SEQ ID NO: 46)

SAFDLAMRIHWIYVFAF;

(SEQ ID NO: 47)

SAFDLAMRINWIYVFAF;

(SEQ ID NO: 48)

SAFDLAMRIYWIYVFAF;

(SEQ ID NO: 49)

SAFDLAMRIMWIYFFAF;

(SEQ ID NO: 50)

SAFDLAMRIMWIYLFAF;

(SEQ ID NO: 51)

SAFDLAMRIMWIYTFAF;

(SEQ ID NO: 52)

SAFDLAMRIMWIYNFAF;

(SEQ ID NO: 53)

SAFDLAMRIMWIYVFAW;

(SEQ ID NO: 55)

HAFDLAMRIMWIYVFAFKRPIPF;

(SEQ ID NO: 56)

SAFDLAMKIMWIYVFAFKRPIPF;

(SEQ ID NO: 57)

SAFDLAMRIHWIYVFAFKRPIPF;

(SEQ ID NO: 58)

SAFDLAMRIHWIYVFAFKRPIPF;

(SEQ ID NO: 59)

SAFDLAMRIYWIYVFAFKRPIPF;

(SEQ ID NO: 60)

SAFDLAMRIMWIYFFAFKRPIPF;

(SEQ ID NO: 61)

SAFDLAMRIMWIYLFAFKRPIPF;

(SEQ ID NO: 62)

SAFDLAMRIMWIYTFAFKRPIPF;

(SEQ ID NO: 63)

SAFDLAMRIMWIYNFAFKRPIPF;

(SEQ ID NO: 64)

SAFDLAMRIMWIYVFAWKRPIPF;

(SEQ ID NO: 65)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAEAVLQAVYETESAFD

LAMRIMWIYVFAFKRPIPFPHAQKLARRLLELKQAASSPLPLE;

(SEQ ID NO: 66)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAEAVLQAVYETESAFD

LAMRIMWIYAFAFNRPIPFSHAQKLARRLLELKQAASSPLPLE;

(SEQ ID NO: 67)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAEAVLQAVYETEDAFD

LAMRIMWIYVFAFNRPIPFSHAQKLARRLLELKQAASSPLPLE;

(SEQ ID NO: 68)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAEAVLQAVYETESAFD

LAMRIMWIYVFAFNRPIPFSHAQKLARRLLELKQAASSPLPLE;

(SEQ ID NO: 69)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDDEAAAVLQAVYETNHAFD

LAMRIHWIYVFAFKRKIPFLHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 70)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAAAVLKAVYATNSAFD

LAMRIIWIYVFAYKRKIPFAHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 71)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDFEADKVLQAVYETNSAFD

LAMRINWIYVFAFKRPIPFVHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 72)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAAAVLKAVYETNSAFD

LAMRINWIYVFAFKRKIPFAHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 73)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEADKVLQAVYDTNSAFD

LAMTIHWIYNFAFKRKIPFLHAPKLARRLLELKLAASSPLP;

(SEQ ID NO: 74)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDDEADRVLQAVYETNSAFD

LAMRINWIYVFAFKRTIPFAHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 75)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDYEADKVLQAVYETNSAFD

LAMRIHWIYIFAFKRPIPFVHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 76)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEADAVLKAVYETNSAFD

LAMRIHWIYNFAFKRKIPFVHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 77)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDDEADKVLQAVYATNSAFD

LAMRIHWIYNFAYKRTIPFVHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 78)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDDEAARVLKAVYATDSAFD

LAMRIHWIYNFAFKRKIPFLHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 79)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEADKVLQAVYATNSAFD

LAMRIHWIYIFAFKRTIPFIHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 80)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDYEADEVLKAVYATNSAFD

LAMRIHWIYNFAFKRKIPFTHAQKLARRLLELKQAASSPLP;

(SEQ ID NO: 81)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEAAKVLQAVYETNSAFD

LAMKIHWIYNFAFKRTIPFVHAQKLARRLLELKQAASSPLPLE;

and

(SEQ ID NO: 82)

MSNAMDGQQLNRLLLEWIGAWDPFGLGKDAYDVEADKVLQAVYATNSAFD

LAMKIHWIYIFAFKRTIPFIHAQKLARRLLELKQAASSPLP.

11. A method for treating and/or limiting an influenza infection, comprising administering to a subject in need thereof a therapeutically effective amount of the polypeptide of claim 1 , or salts thereof, to treat and/or limit the influenza infection.

12. A method for diagnosing an influenza infection, or monitoring progression of an influenza infection, comprising

(a) contacting a biological sample from a subject suspected of having an influenza infection with a diagnostically effective amount of the polypeptide of claim 1 under conditions suitable for binding of the polypeptide to a viral HA protein present in the sample; and

(b) detecting polypeptide-viral HA binding complexes,

where the presence of such binding complexes indicates that the subject has an influenza infection, or provides a measure progression of an influenza infection.

13. A method for identifying candidate influenza vaccines, comprising

(a) contacting test compounds with the polypeptide of claim 1 under conditions suitable for polypeptide binding;

(b) removing unbound test compounds; and

(c) identifying those test compounds that bind to the polypeptide, wherein such test compounds are candidate influenza vaccines.

14. A method for identifying candidate compounds for treating, limiting, and/or diagnosing influenza infection, comprising

(a) contacting an influenza HA protein with (i) test compounds and (ii) the polypeptide of claim 1 , under conditions suitable for binding of the HA protein to the polypeptide; and

(b) identifying those test compounds that outcompete the polypeptide for binding to the HA protein, wherein such test compounds are candidate compounds for treating, limiting, and/or diagnosing influenza infection.