US2007185027A1PendingUtilityA1
Antiviral agents for the treatment, control and prevention of infections by coronaviruses
Est. expiryApr 28, 2023(expired)· nominal 20-yr term from priority
A61P 31/12A61P 31/14A61P 11/00C12N 2770/20022A61K 38/162C07K 14/005A61K 38/16
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Claims
Abstract
The invention provides compositions and methods that are useful for preventing and treating a coronavirus infection in a subject. More specifically, the invention provides peptides and conjugates and pharmaceutical compositions containing those peptides and conjugates that block fusion of a coronavirus, such as the SARS virus, to a target cell. This blocking mechanism prevents or treats a coronavirus infection, such as a SARS infaction, in a subject, such as a human subject.
Claims
exact text as granted — not AI-modified1 . An antiviral peptide having between 7 and 50 amino acids, wherein said peptide exhibits antiviral activity against a coronavirus, and where said peptide contains a sequence comprising at least 7 contiguous amino acids from one of the following sequences:
(SEQ ID NO: 1)
DV DL GD I SG I NAS V VN I QKE I DR L NE VA KN L NES L IDLQE LG K Y EQY I K;
(SEQ ID NO: 2)
QIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT;
(SEQ ID NO: 3)
ESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISS;
(SEQ ID NO: 4)
GKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAE;
and
(SEQ ID NO: 5)
RLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDF.
2 . The peptide of claim 1 , wherein said peptide contains a sequence selected from the group consisting of
SVVNIQK
VVNIQKE
VNIQKEI
(SEQ ID NO: 6)
(SEQ ID NO: 7)
(SEQ ID NO: 8)
NIQKEID
IQKEIDR
QKEIDRL
(SEQ ID NO: 9)
(SEQ ID NO: 10)
(SEQ ID NO: 11)
KEIDRLN
EIDRLNE
IDRLNEV
(SEQ ID NO: 12)
(SEQ ID NO: 13)
(SEQ ID NO: 14)
DRLNEVA
RLNEVAK
LNEVAKN
(SEQ ID NO: 15)
(SEQ ID NO: 16)
(SEQ ID NO: 17)
NEVAKNL
EVAKNLN
VAKNLNE
(SEQ ID NO: 18)
(SEQ ID NO: 19)
(SEQ ID NO: 20)
AKNLNES
KNLNESL
NLNESLI
(SEQ ID NO: 21)
(SEQ ID NO: 22)
(SEQ ID NO: 23)
LNESLID
NESLIDL
ESLIDLQ
(SEQ ID NO: 24)
(SEQ ID NO: 25)
(SEQ ID NO: 26)
SLIDLQE
LIDLQEL
IDLQELG
(SEQ ID NO: 27)
(SEQ ID NO: 28)
(SEQ ID NO: 29)
DLQELGK
LQELGKY
QELGKYE
(SEQ ID NO: 30)
(SEQ ID NO: 31)
(SEQ ID NO: 32)
ELGKYEQ
LGKYEQY
GKYEQYI
(SEQ ID NO: 33)
(SEQ ID NO: 34)
(SEQ ID NO: 35)
KYEQYIK
QIPFAMQ
IPFAMQM
(SEQ ID NO: 36)
(SEQ ID NO: 37)
(SEQ ID NO: 38)
PFMAQMA
FAMQMAY
AMQMAYR
(SEQ ID NO: 39)
(SEQ ID NO: 40)
(SEQ ID NO: 41)
MQMAYRF
QMAYRFN
MAYRFNG
(SEQ ID NO: 42)
(SEQ ID NO: 43)
(SEQ ID NO: 44)
AYRFNGI
YRFNGIG
RFNGIGV
(SEQ ID NO: 45)
(SEQ ID NO: 46)
(SEQ ID NO: 47)
FNGIGVT
NGIGVTQ
IGVTQNV
(SEQ ID NO: 48)
(SEQ ID NO: 49)
(SEQ ID NO: 50)
GVTQNVL
VTQNVLY
TQNVLYE
(SEQ ID NO: 51)
(SEQ ID NO: 52)
(SEQ ID NO: 53)
QNVLYEN
NVLYENQ
VLYENQK
(SEQ ID NO: 54)
(SEQ ID NO: 55)
(SEQ ID NO: 56)
LYELNQKQ
YENQKQI
ENQKQIA
(SEQ ID NO: 57)
(SEQ ID NO: 58)
(SEQ ID NO: 59)
NQKQIAN
QKQIANQ
KQIANQF
(SEQ ID NO: 60)
(SEQ ID NO: 61)
(SEQ ID NO: 62)
QIANQFN
IANQFNK
ANQFNKA
(SEQ ID NO: 63)
(SEQ ID NO: 64)
(SEQ ID NO: 65)
NQFNKAI
QFNKAIS
FNKAISQ
(SEQ ID NO: 66)
(SEQ ID NO: 67)
(SEQ ID NO: 68)
NKAISQI
KAISQIQ
AISQIQE
(SED ID NO: 69)
(SEQ ID NO: 70)
(SEQ ID NO: 71)
ISQIQES
SQIQESL
QIQESLT
(SEQ ID NO: 72)
(SEQ ID NO: 73)
(SEQ ID NO: 74)
ESLTTTS
SLTTTST
LTTTSTA
(SEQ ID NO: 75)
(SEQ ID NO: 76)
(SEQ ID NO: 77)
TTTSTAL
TTSTALG
TSALGAK
(SEQ ID NO: 78)
(SEQ ID NO: 79)
(SEQ ID NO: 80)
STALGKL
TALGKLQ
ALGKLQD
(SEQ ID NO: 81)
(SEQ ID NO: 82)
(SEQ ID NO: 83)
LGKLQDV
GKLQDVV
KLQDVVN
(SEQ ID NO: 84)
(SEQ ID NO: 85)
(SEQ ID NO: 86)
LQDVVNQ
QDVVNQN
DVVNQNA
(SEQ ID NO: 87)
(SEQ ID NO: 88)
(SEQ ID NO: 89)
VVNQNAQ
VNQNAQA
NQNAQAL
(SEQ ID NO: 90)
(SEQ ID NO: 91)
(SEQ ID NO: 92)
QNTAQALN
NAQALNT
AQALNTL
(SEQ ID NO: 93)
(SEQ ID NO: 94)
(SEQ ID NO: 95)
QALNTLV
ALNTLVK
LNTLVKQ
(SEQ ID NO: 96)
(SEQ ID NO: 97)
(SEQ ID NO: 98)
NTLVKQL
TLVKQLS
LVKQLSS
(SEQ ID NO: 99)
(SEQ ID NO: 100)
(SEQ ID NO: 101)
VKQLSSN
KQLSSNF
QLSSNFG
(SEQ ID NO: 102)
(SEQ ID NO: 103)
(SEQ ID NO: 104)
LSSNFGA
SSNFGAI
SNFGAIS
(SEQ ID NO: 105)
(SEQ ID NO: 106)
(SEQ ID NO: 107)
NFGAISS
LQDVVNQ
QDVVNQN
(SEQ ID NO: 108)
(SEQ ID NO: 109)
(SEQ ID NO: 110)
DVVNQNA
VVNQNAQ
VNQNAQA
(SEQ ID NO: 111)
(SEQ ID NO: 112)
(SEQ ID NO: 113)
NQNAQAL
QNAQALN
NAQALNT
(SEQ ID NO: 114)
(SEQ ID NO: 115)
(SEQ ID NO: 116)
AQALNTL
QALNTLV
ALNTLVK
(SEQ ID NO: 117)
(SEQ ID NO: 118)
(SEQ ID NO: 119)
LNTLVKQ
NTLVKQL
TLVKQLS
(SEQ ID NO: 120)
(SEQ ID NO: 121)
(SEQ ID NO: 122)
LVKQLSS
VKQLSSN
KQLSSNF
(SEQ ID NO: 123)
(SEQ 1D NO: 124)
(SEQ ID NO: 125)
QLSSNFG
LSSNFGA
SSNFGAI
(SEQ ID NO: 126)
(SEQ ID NO: 127)
(SEQ ID NO: 128)
SNFGAIS
NEGAISS
FGAISSV
(SEQ ID NO: 129)
(SEQ ID NO: 130)
(SEQ ID NO: 131)
GAISSVL
AISSVLN
ISSVLND
(SEQ ID NO: 132)
(SEQ ID NO: 133)
(SEQ ID NO: 134)
SSVLNDI
SVLNDIL
VLNDILS
(SEQ ID NO: 135)
(SEQ ID NO: 136)
(SEQ ID NO: 137)
LNDILSR
NDILSRL
DILSRLD
(SEQ ID NO: 138)
(SEQ ID NO: 139)
(SEQ ID NO: 140)
ILSRLDK
LSRLDK
SRLDKV
(SEQ ID NO: 141)
(SEQ ID NO: 142)
(SEQ ID NO: 143)
RLDKVE
LDKVEA,
RLITGRL
(SEQ ID NO: 144)
(SEQ ID NO: 145)
(SEQ ID NO: 146)
LITGRLQ
ITGRLQS
TGRLQSL
(SEQ ID NO: 147)
(SEQ ID NO: 148)
(SEQ ID NO: 149)
GRLQSLQ
RLQSLQT
LQSLQTY
(SEQ ID NO: 150)
(SEQ ID NO: 151)
(SEQ ID NO: 152)
QSLQTYV
SLQTYVT
LQTYVTQ
(SEQ ID NO: 153)
(SEQ ID NO: 154)
(SEQ ID NO: 155)
QTYVTQQ
TYVTQQL
YVTQQLI
(SEQ ID NO: 156)
(SEQ ID NO: 157)
(SEQ ID NO: 158)
VTQQLIR
TQQLIRA
QQLIRAA
(SEQ ID NO: 159)
(SEQ ID NO: 160)
(SEQ ID NO: 161)
QLIRAAE
LIRAAEI
IRAAEIR
(SEQ ID NO: 162)
(SEQ ID NO: 163)
(SEQ ID NO: 164)
RAAEIRA
AAEIRAS
AEIRASA
(SEQ ID NO: 165)
(SEQ ID NO: 166)
(SEQ ID NO: 167)
EIRASAN
IRASANL
RASANLA
(SEQ ID NO: 168)
(SEQ ID NO: 169)
(SEQ ID NO: 170)
ASANLAA
SANLAAT
ANLAATK
(SEQ ID NO: 171)
(SEQ ID NO: 172)
(SEQ ID NO: 173)
NLAATKM
LAATKMS
AATKMSE
(SEQ ID NO: 174)
(SEQ ID NO: 175)
(SEQ ID NO: 176)
ATKMSEC
TKMSECV
KMSECVL
(SEQ ID NO: 177)
(SEQ ID NO: 178)
(SEQ ID NO: 179)
MSECVLG.
(SEQ ID NO: 180)
3 . A peptide according to claim 1 , wherein said peptide comprises at least 10, 15, 20, 25, 30, 35, or 40 contiguous amino acids from one of the sequences:
(SEQ ID NO: 181)
VVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK;
(SEQ ID NO: 2)
QIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT;
(SEQ ID NO: 3)
ESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISS;
(SEQ ID NO: 4)
GKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAE;
and
(SEQ ID NO: 5)
RLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDF.
4 . The peptide according to claim 1 , wherein said peptide is linked to a carrier protein.
5 . The peptide according claim 4 , wherein said peptide is linked to human serum albumin.
6 . An antiviral peptide having between 7 and 50 amino acids, wherein said peptide exhibits antiviral activity against a coronavirus, and wherein said peptide has the structure:
B-X-Z, where B is an amino acid sequence containing up to about 43 amino acids, or B is an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecule carrier group, or B is a carrier protein, in which case B may contain more than 8 sequence to said carrier protein; Z is an amino acid sequence containing up to about 43 amino acids, or Z comprises a carboxyl group, an amindo group, a hydrophobic group, or a macromolecular carrier group, or Z is a carrier protein, such as HSA, in which case Z may contain more than 8 amino acids, and may also comprises a linker peptide sequence that connects the antiviral sequence to said carrier protein; wherein when considered together B and Z must contain at least 8 amino acids between the B and Z group; and wherein X is a peptide sequence comprising at least 7 contiguous amino acids from one of the following sequences: (SEQ ID NO: 181) VVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK; (SEQ ID NO: 2) QIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT; (SEQ ID NO: 3) ESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISS; (SEQ ID NO: 4) GKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAE; and (SEQ ID NO: 5) RLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDF.
7 . The peptide according to claim 6 , comprising at least 10, 15, 20, 25, 30, 35, or 40 contiguous amino acids from one of the following sequences:
(SEQ ID NO: 181)
VVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK;
(SEQ ID NO: 2)
QIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT;
(SEQ ID NO: 3)
ESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISS;
(SEQ ID NO: 4)
GKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAE;
and
(SEQ ID NO: 5)
RLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDF.
8 . An antiviral peptide having between 7 and 50 amino acids, wherein said peptide exhibits antiviral activity against a coronavirus, and wherein said peptide comprises a sequence that exhibits identity in any two of the seven positions of a contiguous heptapeptide, wherein said contiguous heptapeptide comprises 7 contiguous amino acids from one of the following sequences:
(SEQ ID NO: 181)
VVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIK;
(SEQ ID NO: 2)
QIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT;
(SEQ ID NO: 3)
ESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISS;
(SEQ ID NO: 4)
GKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAE;
and
(SEQ ID NO: 5)
RLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDF.
9 . The peptide according to claim 8 , wherein said sequence identity is located in the ith and i+4th positions in said contiguous heptapeptides.
10 . A pharmaceutical composition comprising a peptide according to claim 1 and a pharmaceutically acceptable diluent, adjuvant and/or excipient.
11 . A method of treating or preventing a coronavirus infection in a subject, comprising administering to a patient suspected of suffering from said infection an effective amount of a peptide or composition according to claim 10 .
12 . The method according to claim 11 , wherrein said subject is a human.
13 . The method according to claim 11 , wherein said subject is a cow, pig, or chicken.
14 . An antiviral peptide having between 7 and 50 amino acids, wherein said peptide exhibits antiviral activity against a coronavirus, and wherein said peptide contains a sequence comprising at least 7 contiguous amino acids from the sequence:
(SEQ ID NO: 1)
DV DL GD I SG I NAS V VN I QKE I DR L NE VA KN L NES L IDLQE LG K Y EQY I K;
wherein the amino acids at bold letter positions can be substituted with an amino acid selected from the group consisting of I, L, V, W, Y, F, N, Q, S, T, D, E, G, H, and M, and wherein amino acids in non-bold positions can be any amino acid except proline.
15 . A compound comprising a peptide according to claim 14 covalently linked to a carrier protein.
16 . The peptide according to claim 14 wherein at least 8 of said amino acids at said bold letter positions are selected from the group consisting of I, L, V, W, and Y.
17 . A compound according to claim 15 wherein said compound is a fusion protein.
18 . A compound according to claim 15 wherein said peptide is linked to said carrier protein by a non-peptide linker.
19 . A pharmaceutical composition comprising a peptide according to claim 14 and a pharmaceutically acceptable excipient, diluent or adjuvant.
20 . A method of preventing or treating a coronavirus infection in a subject, comprising administering to said subject a pharmaceutical composition according to claim 19.Cited by (0)
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