Table 3 HR2-based peptides impeding the HR1-HR2 interaction

From: Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines

Name

Sequence

IC50s of viral S-mediated cell-cell fusion (nM)

IC50s of pseudotyped coronaviruses (nM)

IC50s of live coronaviruses (nM)

Protective efficacy

Stage

Refs.

2019-nCoV-HR2P

D1168ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL1203

WT: 180 VS EK1:190

WT: 980 VS EK1: 2380

N.A.

N.A.

 

72

OC43-HR2P

SLDYINVTFLDLQVEMNRLQEAIKVLNQSYINLKDI

SARS-CoV: 540, MERS-CoV: 390, HCoV-OC43: 660, HCoV-229E: 840, HCoV-NL63: 940

WT > 1270

HCoV-OC43: 930

N.A.

 

75

HY3000

P3

I1169SGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL1203

P3

SARS-CoV-2: 720

IC50s of WT, Alpha, Beta, Gamma, Kappa, and Delta.

P3: 780, 890, 960, 450, 1250, and 1390, respectively. P3-1: 370, 540, 360, 110, 190, and 190, respectively. P3-2: 340, 800, 230, 140, 600, and 270, respectively. P3-3: 230, 370, 100, 110, 430, and 320, respectively. P3-4: 240, 590, 200, 220, 480, and 550, respectively. P4-5: 1590, 1430, 1240, 630, 1060, and 1820, respectively.

WT: 580

N.A.

Clinical trials

81

(PN: CN 114437184 B)

P3-1

ISGINASVVNIQKEIDRLNEVAKNLNESLIDLKEL

P3-2

VDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL

P3-3

VKFGDISGINASVVNIKEEIDRLYEVVKNLNESLIDLQEL

P3-4

ISGINASVVNIKEEIDRLNEVAKNLNESLIDLQEL

P3-5

ISGINASVVNIQKEIDRLNEVAKELNESLIDLQEL

EK1

SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKEL

WT: 315.0, B.1.1.529: 95, SARS-CoV: 409.3, MERS-CoV: 239.5, HCoV-OC43: 787.6, HCoV-229E: 207.4, HCoV-NL63: 751.0

WT: 1270, Alpha: 1240, Gamma (B.1.1.248): 1250, Omicron: 309, SARS-CoV: 3237, MERS-CoV: 631.8, HCoV-OC43: 1398, HCoV-229E: 3963, HCoV-NL63: 7666, WIV1: 5425, Rs3367: 6014

WT: 2468, Omicron: 1138, MERS-CoV: 802.1, HCoV-OC43: 1554, HCoV-229E: 4375, HCoV-NL63: 3693

Intranasal application of EK1 can prevent and treat infection in mice challenged with HCoV-OC43, MERS-CoV, and SARS-CoV-2

Clinical trials

75,76,77,78

EK1C4

EK1-GSGSG-PEG4-Chol

WT: 1.3, Omicron: 0.9, SARS-CoV: 4.3, MERS-CoV: 2.5, HCoV-OC43: 7.7, HCoV-229E: 5.2, HCoV-NL63: 21.4

WT: 5.7, Alpha: 5.5, Gamma (B.1.1.248): 6.5, Omicron: 8.6, SARS-CoV: 11.7, MERS-CoV: 11.1, HCoV-OC43: 37.7, HCoV-229E: 12.4, HCoV-NL63: 76.6, WIV1: 30.8, Rs3367: 66.9

WT: 36.6, Omicron: 85.4, MERS-CoV: 4.2, OC43: 24.8, HCoV-229E: 101.5, HCoV-NL63: 187.6

Intranasal application of EK1 can prevent and treat infection in mice challenged with HCoV-OC43 and SARS-CoV-2

 

76,77,78

EKL1C

EK1-GSG-Chol

WT: 8.0, B.1.1.529: 5.5

WT: 37.0, Alpha: 12.0, Gamma (P1): 46.0, B.1.1.529: 26.1, SARS-CoV: 76.0, MERS-CoV: 48.0, HCoV-OC43: 668, HCoV-NL63: 35.0, WIVI: 218.0, Rs3367: 46.0

WT: 3.0, Omicron: 182.2, HCoV-OC43: 281

Intranasal application of EKL1C can prevent and treat infection in mice challenged with SARS-CoV-2 and HCoV-OC43

 

77,89

EK1C16

EK1-GSGSG-PEG4-C16

MERS-CoV: 10.0, HCoV-OC43: 10.0

WT: 480, Alpha: 190, Beta: 430, Gamma (B.1.1.248): 260, Delta: 110, Omicron: 230, MERS-CoV: 100, SARS-CoV: 170, WIV1: 150, Rs3367: 300

HCoV-OC43: 70.0, Omicron: 750

N.A.

 

93

EK1P4HC

EK1-GSGSG-PEG4-25-HC

N.A.

WT: 800, Alpha: 2280, Beta: 620, Gamma (B.1.1.248): 480, Delta: 110, SARS-CoV: 350, MERS-CoV: 100

HCoV-OC43: 410, HCoV-229E: 480

Preventing and treating infection in mice challenged with HCoV-OC43

 

94

IPB02

ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELK (Chol)

WT: 31.6, D614G: 27.7

WT: 148.8, D614G: 88.1, SARS-CoV: 304, MER-CoV: 642, HCoV-NL64: 568.9, HCoV-229E: 604.8

N.A.

N.A.

 

86

IPB02V1

ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-PEG8-K (Chol)

WT: 1.1,

D614G: 0.6

WT: 14.3, D614G: 21.5, SARS-CoV: 33.6, MER-CoV: 66.9, HCoV-NL64: 62.5, HCoV-229E: 203.9

IPB02V2

DISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-PEG8-K (Chol)

WT: 0.6, D614G: 0.4

WT: 18.1, D614G: 20.8, SARS-CoV: 56.5, MER-CoV: 55.3, HCoV-NL64: 67.5, HCoV-229E: 535.7

IPB02V3

EISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL-PEG8-K (Chol)

WT: 0.4,

D614G: 0.2

WT: 17.5, D614G: 14.4, SARS-CoV: 48, MER-CoV: 38.5, HCoV-NL64: 75.8, HCoV-229E: 545.7

IPB02V4

ELSGINASVVNLQKEIDRLNEVAKNLNESLIDLQEL-PEG8-K (Chol)

WT: 0.3,

D614G: 0.1

WT: 15.2, D614G: 26.3, SARS-CoV: 63, MER-CoV: 22.4, HCoV-NL64: 66.3, HCoV-229E: 502

IPB02V5

SLTQINASVVNLQKEIDRLNEVAKNLNESLIDLQEL-PEG8-K (Chol)

WT: 2.1,

D614G: 1.3

WT: 23.5, D614G: 27.5, SARS-CoV: 65.9, MER-CoV: 68.4, HCoV-NL64: 70.8, HCoV-229E: 1128.4

MERS-LP

SLTQINTTLLDLTYEMLSLQQVVKALNESYIDLKEL-PEG8-K (Chol)

WT: 102.9,

D614G: 79.1

MERS-CoV: 82.9; WT, D614G, SARS-CoV, HCoV-NL64, and HCoV-229E: more than 2500

OC43-LP

SLDYINVTFLDLQDEMNRLQEAIKVLNQSYINLKDI-PEG8-K (Chol)

WT: 4.1,

D614G: 2.4

WT: 82.8, D614G: 97.5, SARS-CoV: 250.4, MER-CoV: 5.2, HCoV-NL64: 416.5, HCoV-229E: 2008.8

EK1V1

SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKELLK (Chol)

WT: 273.5,

D614G: 214.5

WT: 2672, D614G: 1790, SARS-CoV: 4370, MER-CoV: 500, HCoV-NL64: 487, HCoV-229E: 1255.6

EK1V2

SLDQINVTFLDLEYEMKKLEEAIKKLEESYIDLKELL--PEG8-K (Chol)

WT: 0.9,

D614G: 0.5

WT: 87.2, D614G: 106.5, SARS-CoV: 252, MER-CoV: 1.1, HCoV-NL64: 59.4, HCoV-229E: 503.3

longHR2_42

P1162DVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQ1201

WT: 1.3

WT: 1.1, Delta: 0.9, Omicron: 4.1

WT: 1.5, Alpha: 0.6, Delta: 5; Omicron: 15.6

N.A.

 

80

longHR2_45

K1157NHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQ1201

WT: 1.6

N.A.

N.A.

N.A.

 

80

[SARSHRC-PEG4]2-chol

HRC-PEG4-chol-PEG4-HRC

The sequence of HRC:

D1168ISGINASVVNIQKEIDRLNEVAKNLNESLIDLQEL1203

For WT, D614G, Alpha, Beta, SARS-CoV: 3~10

WT: ~300 (VeroE6 cells), ~5 (VeroE6-TMPRSS2 cells)

 

It can prevent SARS-CoV-2 transmission in ferrets by intranasal application

 

87

  1. WT, wild type (of SARS-CoV-2). N.D., indicates below neutralizing threshold. N.A., not application. PN, patent number. CN, China
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