Table 1 Representative cross-inhibitory nAbs targeting fusion peptide

COV44-62

COVID-19 convalescents

IGHV1-1: ASLLIVGGFDPLDDFEV, IGKV2-8: SSYGGTNNLL

P₈₁₂SKRSFIEDLLFNK₈₂₅ in FP

Binding to the uncovered S2ʹ site and FP after S1 dissociation, inhibiting S2ʹ cleavage and/or preventing FP insertion into host cell membrane

Inhibition of SARS-CoV-2 S-mediated membrane fusion

WT: 9.80, Alpha: 11.24, Beta: 7.06, Gamma: 12.80, Delta: 13.28, Mu: 6.52, Omicron-BA.1: 10.38, Omicron-BA.2: 20.26, SARS-CoV: 6.37, MERS-CoV: 25.48, HCoV-NL63: 1.06, HCoV-229E: 2.11

HCoV-OC43: 22.9

COV44-62 hardly limits SARS-CoV-2 infection in the Syrian hamster model

⁵¹

COV44-79

IGHV3-30: AILIIPGITEPGSPDALDI, IGKV1-12: QQASSFPWSIT

P₈₁₂SKRSFIEDLLF₈₂₃ in FP

WT: 21.53, Alpha: 24.21, Beta: 19.66, Gamma: 30.64, Delta: 45.33, Mu: 16.51, Omicron-BA.1: 33.02, Omicron-BA.2: 55.44, SARS-CoV: 20.91, HCoV-NL63: 3.24, HCoV-229E: 56.19, MERS-CoV>100

HCoV-OC43: 28.4

COV44-79 can limit SARS-CoV-2 infection in the Syrian hamster model

⁵¹

VN01H1

COVID-19 convalescents and vaccinated individuals

IGHV3-64: VKNSDVFRFPHLYFDV, IGKV3-15: QQYDNWPSIT

R₈₁₅SFIEDLLFN₈₂₄ in FP

WT: N.D., PDF-2180: 2.7 (in the absence of TMPRSS2); WT: 28.8, SARS-CoV: 16.1, MERS-CoV: 31.3, HCoV-NL63: 2.7, HCoV-229E: 2.5, WIV1: 0.4 (in the presence of TMPRSS2)

scFv format: WT: 7.3, BA.1: 0.9, BA.2: 2.6; IgG format: WT: 43.0, BA.1: 12.5, BA.2: 19.7

Preventing SARS-CoV-2 Gamma infection and reducing viral burden in the Syrian hamster

⁵²

VP12E7

IGHV3-64: VKGLDVLRFLDLSTPSGERLDAFDI, IGKV1-9: QQLNSYPLFT

R₈₁₅SFIEDLLFNK₈₂₅ in FP

WT N.D., PDF-2180: 13.5 (in the absence of TMPRSS2); WT: 113.8, SARS-CoV: 24.1, MERS-CoV: 84.4, HCoV-NL63: 2.7, HCoV-229E: 13.6, WIV1: 8.0 (in the presence of TMPRSS2)

N.A

N.A

⁵²

C77G12

IGHV3-30: ARGSDYVDDSPPLHY,

IGKV1-16: QQYDSFPFT

K₈₁₄RSFIEDLLF₈₂₃ in FP

WT: 3.7, PDF-2180: N.D (in the absence of TMPRSS2); WT: 37.6, SARS-CoV: 37.6, MERS-CoV: 83.2, WIV1: 1.2, HCoV-NL63: N.D., HCoV-229E: N.D. (in the presence of TMPRSS2)

scFv format: WT: 2.0, BA.1: 0.6, BA.2: 0.8; IgG format: WT: 25.9, BA.1: 2.9, BA.2: 5.4

Preventing SARS-CoV-2 Gamma infection and reducing viral burden in the Syrian hamster

⁵²

76E1

COVID-19 convalescents

IGHV3-43: AALVIVAAGDDFDL, IGKV3-43: CSYGGRNNLI

R₈₁₅SFIEDLLFNK₈₂₅ in FP

WT: 0.42, SARS-CoV: 4.8, MERS-CoV: 3.8, HCoV-229E: 1.2, HCoV-NL63: N.D., HCoV-OC43: N.D.

WT: 0.37, HCoV-229E: 1.6, HCoV-NL63: 3.9, HCoV-OC43: 4.6, SARS-CoV and MERS-CoV: N.D.

Preventing and treating SARS-CoV-2 and HCoV-OC43 infections in mice

⁵³

Fp.006

COVID-19 convalescents

IGHV3-30: DLFLSDYDRSGYDPTRGGFDH,

IGKV3-15: QQYGDWPLVT

S₈₁₃KRSFIEDLLFNK₈₂₅ in FP

WT: 0.7, Alpha: 15.6, Beta: 29.6, Gamma: 0.4, Delta: 50, Omicron-BA.1: 19.1, BA.2: N.D., BA.2.72: 80, BA.2.75.2: 30, BA.4/BA.5: N.D., WT: 3.1 (on cells with TMPRSS2)

N.A.

Preventing SARS-CoV-2 infection in mice

⁵⁴