Table 2 Representative cross-inhibitory nAbs targeting stem helix
Names | Sources | V-class and CDR3-sequence | Binding epitope | Neutralizing mechanism | Binding affinity to viral S protein (nM) | S-mediated cell-cell fusion | IC50s of pseudotyped coronaviruses (μg/ml) | IC50s of live coronaviruses (μg/ml) | Protective efficacy | Refs |
|---|---|---|---|---|---|---|---|---|---|---|
S2P6 | COVID-19 convalescent donors | IGHV1-46: ARGSPKGAFDY, IGKV3-20: QQYGSSPPRFT | D1146SFKEELDKYFKNH1159 | Disturbing stem helical bundle, blocking 6-HB formation, and preventing virus-host membrane fusion | SARS-CoV-2: 7, SARS-CoV: 7, MERS-CoV: 12, HCoV-OC43: 16, HKU1:~120 | Inhibition SARS-CoV-2 S-mediated membrane fusion | SARS-CoV-2: 1.4, SARS-CoV: 2.4, MERS-CoV: 17.1, HCoV-OC43: 1.3, PANG/GD: 0.02; Gamma, Alpha, Beta, and Kappa: 0.7~3.0 | SARS-CoV-2: 1.67 (in VeroE6-TMPRSS2 cells) | Prophylactic use of S2P6 can reduce viral burden in the Syrian hamster challenged with SARS-CoV-2 | |
CC40.8 | IGHV3-23: AITMAPVV, IGKV3-10: YSTDSSGNHAV | Q1142PELDSFKEELDKYFKNH1159 | SARS-CoV-2 < 0.001 | WT, Gamma, Alpha, Beta, and Delta: 6.0~13.0; SARS-CoV: 15.0; SHC014: 1.0; PANG: 14.0, WIV1: 6.0, MERS-CoV>300 | N.A. | Prophylactic use of CC40.8 can reduce viral burden in mice and Syrian hamster challenged with SARS-CoV-2 | ||||
CV3-25 | IGHV5-51: LPQYCSNGVCQRWFDP, IGKV1-12: QQGNSFPYT | D1153KYFKNHTSPDVDL1166 | SARS-CoV-2: 0.6 | N.A. | WT, Alpha, Beta, Delta, Gamma, Omicron, WIV1, and SARS-CoV: ~0.1 to ~0.8 | N.A. | N.A. | |||
hr2.016 | IGHV3-23: AKLLVVFVIDY, IGKV3-20: QQYGSSPPT | E1144LDSFKEELDKYFKNHTS1161 | SARS-CoV-2 (e.g., WT, Delta, Omicron BA.1, and BA.4/5) and MERS-CoV: 29.3 to 104.7 ng/mL | N.A. | WT: 0.01, Alpha: 0.3, Beta: ~0.5, Gamma: ~0.6×10−3, Delta: 0.3, Omicron-BA.1: ~0.5, BA.2: ~0.6, BA.2.72: ~1.1, BA.2.75.2: ~0.9, BA.4/BA.5: ~0.9, WT: 1.2×10−2 (on cells with TMPRSS2) | N.A. | Preventing SARS-CoV-2 infection in mice | |||
CC25.106 | COVID-19 convalescent-vaccinated donors | IGHV1-46: ARGGVHGLDY, IGKV1-51: GTWDTNLGAFV | F1148KEELDKYFKN1158 | SARS-CoV-2: 0.98, MERS-CoV: 0.59 | N.A. | WT: 3.8, SARS-CoV: 12, WIV1: 16, PANG17: 36, SHC014: 0.8, MERS-CoV: 3.3, Alpha: 9.3, Beta: 27, Gamma: 20, Delta: 25, Various Omicron subvariants: 14~43 | N.A. | Preventing SARS-CoV-2, SARS-CoV, and MERS-CoV infections in mice | ||
CC95.108 | IGHV1-46: ARDSRGPGIF, IGKV1-51: GAWDSTPGTWV | SARS-CoV-2: 0.63, MERS-CoV: 1.79 | N.A. | WT: 1.5, SARS-CoV: 7.5, WIV1: 7.1, PANG17: 13, SHC014: 0.5, MERS-CoV: 0.5, Alpha: 2.8, Beta: 5.9, Gamma: 2.1, Delta: 6.9, Omicron subvariants: 4.3~12 | N.A. | N.A. | ||||
CC68.109 | IGHV1-46: ARGSNWGPWDY, IGKV3-20: QQYDSSPPIFT | SARS-CoV-2: 1.15, MERS-CoV: 8.8 | N.A. | WT: 2.0, SARS-CoV: 14, WIV1: 18, PANG17: 35, SHC014: 1.6, MERS-CoV: 2.3 | N.A. | Preventing SARS-CoV-2, SARS-CoV, and MERS-CoV infections in mice | ||||
CC99.103 | IGHV1-46: ASGILTGLFDY, IGKV3-20: LQYGSSPPIFT | SARS-CoV-2: 0.43, MERS-CoV: 3.2 | N.A. | WT: 5.1, SARS-CoV: 4.4, WIV1: 6.3, PANG17: 12, SHC014: 0.3, MERS-CoV: 1.5, Alpha: 5.8, Beta: 12, Gamma: 14, Delta: 12, Omicron subvariants: 7.5~20 | N.A. | Preventing SARS-CoV-2, SARS-CoV, and MERS-CoV infections in mice | ||||
CC95.102 | IGHV1-46: ARDSRGPGIF, IGKV1-51: GAWDSTPGTWV | MERS-CoV: 3.2 | N.A. | WT: 0.1, SARS-CoV: 1.0, WIV1: 0.9, PANG17: 1.3, SHC014: 0.1 MERS-CoV: >300, Alpha: 0.3, Beta: 0.8, Gamma: 0.2, Delta: 0.4, Omicron subvariants: 0.7~1.8 | N.A. | N.A. | ||||
WS6 | Mice immunized by SARS-CoV-2 S mRNA | IGHV1-5: TRTGSYFDY, IGKV4-61: QQYQSYPPT | F1148KEELDKYFK1157 | N.A | N.A. | WT, Alpha, Beta, Gamma, Delta, Mu, and Omicron: 2.46~26.52; RaTG13, PANG/GD, PANG/GX, SARS-CoV, WIV1, and SHC014: 0.11~4.91; MERS-CoV: N.D. | N.A. | N.A. | ||
B6 | Mice co-immunized with MERS-CoV S and SARS-CoV S antigens | IGHV1-19: ARQLGRGNGLDYW, IGKV8-27: HQYLSSYT | S1147FKEELDKYF1156 | MESR-CoV: 10-3, HCoV-OC43: 10-2, SARS-CoV: 1.0, SARS-CoV-2: 1.0 | N.A. | MERS-CoV: 1.7; HCoV-OC43: 4.0; HKU4: 2.4; SARS-CoV and SARS-CoV-2: N.D. | N.A. | N.A. | ||
28D9 | Humanized mice co-immunized with S antigens from MERS-CoV, SARS-CoV and HCoV-43 | IGHV6-1: ARVPMNRGGMDV, IGKV4-1: HQYYSIPNT | E1150ELDKYFK1157 | N.A. | Inhibition MERS-CoV S-mediated membrane fusion | MERS-CoV: 0.13, SARS-CoV: 60.5, SARS-CoV-2: 45.3, HCoV-OC43: 64.9 | MERS-CoV: 0.93, SARS-CoV-2 and SARS-CoV: N.D. | N.A. | ||
1.6C7 | IGHV6-1: ARATLARGALDY, IGKV4-1: QQYYSTPWT | N.A. | MERS-CoV: 0.39, SARS-CoV>300, SARS-CoV-2 > 300, HCoV-OC43 > 300 | MERS-CoV: 0.08, SARS-CoV-2 and SARS-CoV: N.D. | N.A. | |||||
IgG22 | MERS-CoV spike stabilized stem antigens immunized mice | IGHV1-19: VRGNDYHGRAMDY, IGKV1-99: FQSNYLFT | S1147FKEELDKYF1156 | Fab format: MERS-CoV: 2.9, SARS-CoV: 7.2, SARS-CoV-2: 6.7 | N.A. | N.A. | MERS-CoV: 0.12, SARS-CoV-2: N.D. | Prophylactic use of IgG22 can prevent MERS-CoV and SARS-CoV-2 infections in mice |
