Table 1.
Representative human neutralizing monoclonal antibodies (nAbs) against SARS-CoV-2
| Name | Binding affinity | Neutralization against SARS-CoV-2 infection | Protection from wild-type SARS-CoV-2 infection | References |
|---|---|---|---|---|
| nAbs targeting the NTD of SARS-CoV-2 | ||||
|
4-8 5-7 2-17 4-18 5-24 |
Bound to SARS-CoV-2 S trimer and NTD proteins | Neutralized infection by wild-type pseudotyped (IC50 ≤ 168 ng/ml) and live (IC50 ≤ 33 ng/ml) SARS-CoV-2 | N/A | [44] |
| 4A8 | Bound to SARS-CoV-2 S (KD 0.996 nM) and S1 (KD 92.7 nM) proteins | Neutralized infection by wild-type pseudotyped (EC50 49 μg/ml) and live (EC50 0.61 μg/ml) SARS-CoV-2 | N/A | [55] |
| 89C8 | Bound to SARS-CoV-2 NTD protein | Neutralized pseudotyped SARS-CoV-2 infection (IC50 4.5 nM) | N/A | [61] |
|
S2L28 S2M28 S2X28 S2X333 |
Bound to SARS-CoV-2 and bat RaTG13 S protein NTDs (EC50 < 100 ng/ml); binding to SARS-CoV-2 NTD escape or natural mutants was reduced | Neutralized infection by wild-type pseudotyped (IC50 < 50 ng/ml) and live SARS-CoV-2 (IC50 2–29 ng/ml); neutralization of mutant SARS-CoV-2 was reduced; neutralized bat RaTG13 pseudovirus infection | Prophylactically protected hamsters from SARS-CoV-2 challenge (for S2X333), with reduced viral replication and/or titers in the lung | [41] |
|
COV2-2489 COV2-2676 |
Bound to a common antigenic site in the SARS-CoV-2 NTD | Neutralized infection by wild-type pseudotyped (IC50 38 or 58 ng/ml) and live (IC50 501 or 199 ng/ml) SARS-CoV-2 | Prophylactically and therapeutically protected hACE2-Tg mice from SARS-CoV-2 infection, with reduced weight loss, viral titers, cytokine levels, or chemokine levels | [42, 54] |
| nAbs targeting the RBD of SARS-CoV-2 | ||||
|
P5A-1B8 P5A-1B9 P5A-2G7 P5A-3C12 |
Bound to the SARS-CoV-2 RBD (KD 0.75–3.55 nM), competing with ACE2 binding | Neutralized infection by wild-type pseudotyped (IC50 0.01–0.66 nM) and live (IC50 0.03–1.76 nM) SARS-CoV-2 | N/A | [63] |
|
TAU-2189 TAU-2230 TAU-2303 TAU-1109 |
Bound to the SARS-CoV-2 RBD with or without blocking RBD-ACE2 binding | Neutralized infection by wild-type pseudotyped (IC50 0.05–1.05 μg/ml) and live (IC50 10 μg/ml) SARS-CoV-2 | N/A | [45] |
|
MD45 MD47 MD62 MD65 MD67 |
Bound to SARS-CoV-2 S, S1, and the RBD (KD 0.5–5.8 nM) with or without blocking RBD-ACE2 binding | Neutralized infection of wild-type live (IC50 0.22–13 μg/ml) SARS-CoV-2 | N/A | [48] |
|
COVA1-18 COVA2-15 |
Bound to SARS-CoV-2 S and the RBD, competing with ACE2 binding | Neutralized infection of wild-type pseudotyped (IC50 8 ng/ml) and live (IC50 ≤ 9 ng/ml) SARS-CoV-2 | N/A | [43] |
| IgG1 ab1 | Bound to SARS-CoV-2 S, S1, and the RBD (KD 0.16 nM), competing the binding of the RBD with ACE2 | Neutralized infection of wild-type pseudotyped (IC50 200 ng/ml) and live (IC50 100 ng/ml) SARS-CoV-2 | Prophylactically and/or therapeutically protected wild-type mice from mouse-adapted SARS-CoV-2 infection or hACE2-Tg mice and hamsters from wild-type SARS-CoV-2 infection, with reduced viral titers or replication in the lung, nasal washes, and oral swabs (for hamsters) | [59] |
|
COV2-2196 COV2-2130 COV2-2381 |
Bound to SARS-CoV-2 S trimer and the RBD (EC50 0.1–10 ng/ml), fully blocking RBD-ACE2 binding | Neutralized infection by wild-type pseudotyped (IC50 ≤ 110 ng/ml) and live (IC50 ≤ 107 ng/ml) SARS-CoV-2, showing synergistic effects (for COV2-2196 and COV2-2130) | Prophylactically and/or therapeutically protected AdV-hACE2-transduced mice from SARS-CoV-2 infection or wild-type mice from mouse-adapted SARS-CoV-2 infection, with reduced weight loss, viral replication or inflammation; prophylactically protected NHPs from SARS-CoV-2 replication | [42, 75] |
| CV07-209 | Bound to the SARS-CoV-2 RBD (KD 0.006 nM; EC50 4.1 ng/ml), blocking RBD-ACE2 attachment | Neutralized infection by wild-type live SARS-CoV-2 (IC50 3.1 ng/ml) | Prophylactically and therapeutically protected hamsters from SARS-CoV-2 infection, preventing weight loss and lung pathology | [64] |
|
CC6.29 CC6.30 CC12.1 |
Bound to SARS-CoV-2 S and the RBD, competing with ACE2 binding | Neutralized infection by wild-type (IC50 1–19 ng/ml) or V367F, G476S, and D614G variants of pseudotyped SARS-CoV-2 | CC12.1 prophylactically protected hamsters from SARS-CoV-2 challenge, with reduced weight loss and viral loads | [73] |
|
2-4 2-7 1-20 1-57 2-15 |
Bound to the SARS-CoV-2 S trimer and RBD proteins | Neutralized infection by wild-type pseudotyped (IC50 ≤ 394 ng/ml) and live (IC50 ≤ 57 ng/ml) SARS-CoV-2 | Prophylactically protected hamsters from SARS-CoV-2 infection, with reduced viral titers and replication in the lung | [44] |
|
J08 I14 F05 G12 C14 B07 |
Bound to the SARS-CoV-2 S trimer, S1, and RBD proteins with high potency | Neutralized infection by wild-type, D614G, and B.1.1.7. variants (IC50 3.9–157.5 ng/ml) of live SARS-CoV-2 | An Fc-engineered version of J08 (J08-MUT) prophylactically and therapeutically protected hamsters from SARS-CoV-2 infection in a dose-dependent manner, without weight loss or with reduced weight loss or viral titers in the lung | [62] |
| MV05 | Bound to prototypic (KD 0.403 nM) and mutant SARS-CoV-2 RBDs, disrupting RBD-ACE2 binding | Neutralized infection by wild-type pseudotyped (IC50 0.03 μg/ml) and live (IC50 1 μg/ml) SARS-CoV-2 | An Fc-engineered version (MV05/LALA) prophylactically and therapeutically protected NHPs from SARS-CoV-2 infection, preventing weight loss and viral replication | [74] |
| CB6 | Bound to the SARS-CoV-2 RBD (KD 2.49 nM), blocking its binding with ACE2 | Neutralized infection by wild-type pseudotyped (IC50 23 ng/ml) and live (IC50 36 ng/ml) SARS-CoV-2 | An Fc-engineered version (CB6(LALA)) prophylactically and therapeutically protected NHPs from SARS-CoV-2 infection, with reduced viral titers and limited lung damage | [65] |
| CT-P59 | Bound to the SARS-CoV-2 RBD (KD 0.027 nM) protein, completely blocking its binding with ACE2 | Neutralized infection by wild-type (IC50 8.4 ng/ml) and D614G variant (IC50 5.7 ng/ml) live SARS-CoV-2 | Therapeutically protected ferrets, hamsters, and NHPs from SARS-CoV-2 infection, with reduced viral titers and clinical symptoms | [47] |
| nAbs targeting other regions of the S protein or S trimer of SARS-CoV-2 | ||||
|
2-43 2-51 |
Bound to SARS-CoV-2 non-NTD and non-RBD S protein regions | Neutralized infection by wild-type pseudotyped (IC50 71 or 652 ng/ml) and live SARS-CoV-2 (IC50 3 or 7 ng/ml) | N/A | [44] |
|
I21 J13 D14 |
Bound to SARS-CoV-2 non-RBD S1 protein region | Neutralized infection by wild-type, D614G, and/or B.1.1.7 (IC50 99.2–500 ng/ml) variants of live SARS-CoV-2 | N/A | [62] |
|
0304-3H3 9A1 |
Bound to SARS-CoV-2 S (KD ≤ 2.14 nM) and S2 (KD ≤ 4.52 nM) proteins | Showed moderate-to-no neutralization against infection by wild-type pseudotyped or live SARS-CoV-2 | N/A | [55] |
| L19 | Bound to SARS-CoV-2 S trimer and S2 proteins | Showed low neutralization potency against infection by wild-type (19.8 μg/ml), D614G (IC50 12.5 μg/ml), and B.1.1.7 (9.9 μg/ml) variants of live SARS-CoV-2 | N/A | [62] |
|
H20 I15 F10 F20 |
Bound to SARS-CoV-2 S trimer with low affinity | Showed moderate neutralization potency (IC50 155–492.2 ng/ml) against infection by wild-type and D614G mutant live SARS-CoV-2 | N/A | [62] |
| Multimeric nAbs targeting multiple SARS-CoV-2 proteins | ||||
| 89C8-ACE2 | Bound to SARS-CoV-2 NTD and RBD proteins | Inhibited S1–ACE2 interaction, preventing infection by wild-type pseudotyped (IC50 29 nM) and live (1.7 nM) SARS-CoV-2 | N/A | [61] |
ACE2 angiotensin-converting enzyme 2, AdV-hACE2 adenovirus-expressing hACE2, EC50 half-maximal effective concentration, hACE2-Tg human ACE2 transgenic, IC50 half-maximal inhibitory concentration, KD equilibrium dissociation constant, nAb neutralizing monoclonal antibody, NHP nonhuman primate, NTD N-terminal domain, RBD receptor-binding domain