Representative SARS-CoV And MERS-CoV RBD-Specific Neutralizing Antibodies
Virus neutralizing antibodies induced by vaccines or infected virus play crucial roles in controlling viral infection. Currently developed SARS-CoV- and MERS-CoV-specific nAbs include monoclonal antibodies (mAbs), their functional antigen-binding fragment (Fab), the single-chain variable region fragment (scFv), or single-domain antibodies [nanobodies (Nbs)]. They target S1-RBD, S1-NTD, or the S2 region, blocking the binding of RBDs to their respective receptors and interfering with S2-mediated membrane fusion or entry into the host cell, thus inhibiting viral infections.
Representative SARS-CoV and MERS-CoV RBD-specific nAbs are summarized below.
| Ab name | Source | Neutralizing activity | Neutralizing mechanism | Protective efficacy | Refsb |
|---|---|---|---|---|---|
| S230.15 m396 mAbs | Human | Neutralize human (strains GD03, Urbani, Tor2) and palm civet (strains SZ3, SZ16) SARS-CoV infection | Recognize epitopes (residues 408, 442, 443, 460, 475) on SARS-CoV S1 protein, interfering with RBD–ACE2 receptor interaction | Protect mice against challenge of SARS-CoV (strains Urbani, rGD03, or rSZ16) | [2] |
| S109.8 S227.14 S230.15 mAbs | Human | Neutralize human (Urbani, GZ02, CUHK-W1), palm civet (HC/SZ/61/03), and raccoon dog (A031G) SARS-CoV infectious clones containing S variants | Inhibit the binding of SARS-CoV RBD–ACE2 receptor | Protect mice against challenge of SARS-CoV infectious clones (Urbani, GZ02, HC/SZ/61/03) or mouse-adapted strain (MA15) | [3] |
| 80R scFv, mAb | Human | Neutralize live SARS-CoV (strain Urbani) infection | Recognize epitopes on SARS-CoV S1 (residues 261–672), blocking RBD–ACE2 binding and inhibiting syncytium formation | NA | [4] |
| CR3022 CR3014 scFv, mAb | Human | Neutralize live SARS-CoV (strain HKU-39849) infection; CR3022 could neutralize CR3014 escape variants | Recognize epitopes on SARS-CoV RBD (residues 318–510); CR3022 binds SARS-CoV-2 RBD with high affinity | CR3014 protects ferrets against SARS-CoV (strain HKU-39849) infection | [6] |
| 33G4 35B5 30F9 mAbs | Mouse | Neutralize human (strains GD03, Tor2) and palm civet (SZ3) pseudotyped SARS-CoV infection | Recognize epitopes on SARS-CoV RBD, blocking RBD–ACE2 receptor binding | NA | [5] |
| MERS-27 m336 MERS-GD27 MCA1 mAbs, Fabs | Human | Neutralize divergent strains of pseudotyped and live (strain EMC2012) MERS-CoV infection | Recognize a number of key epitopes on MERS-CoV RBD protein, blocking RBD–DPP4 receptor binding | Prophylactically and therapeutically prevent and treat MERS-CoV (strain EMC2012) challenge in hDPP4-Tg mice, rabbits, or common marmosets | [7,8] |
| 4C2 h hMS-1 mAbs | Humanized | Neutralize divergent strains of pseudotyped and live (strain EMC2012) MERS-CoV infection | Recognize epitopes (residues 510, 511, 553) on MERS-CoV RBD protein, blocking RBD–DPP4 receptor binding | Prevent MERS-CoV (strain EMC2012) challenge in Ad5/hDPP4-transduced or hDPP4-Tg mice | [7] |
| Mersmab1 4C2 D12 mAbs | Mouse | Neutralize pseudotyped and live (strain EMC2012) MERS-CoV infection | Recognize a number of key epitopes on MERS-CoV RBD protein, blocking RBD–DPP4 receptor binding | NA | [7] |
| HCAb-83 Nb | Dromedary camel | Neutralizes live MERS-CoV (strain EMC2012) infection | Recognizes epitope (residue 539) on MERS-CoV RBD protein | Prophylactically prevents MERS-CoV (strain EMC2012) challenge in hDPP4-Tg mice | [8] |
| NbMS10-Fc Nb | Llama | Neutralizes multiple strains of pseudotyped and live (strain EMC2012) MERS-CoV infection | Recognizes epitope (residue 539) on MERS-CoV RBD protein | Prophylactically and therapeutically prevents and treats MERS-CoV (strain EMC2012) challenge in hDPP4-Tg mice | [8] |
Ref:
[1]Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses
[2]Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies
[3]Structural basis for potent cross-neutralizing human monoclonal antibody protection against lethal human and zoonotic severe acute respiratory syndrome coronavirus challenge
[4]Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association
[5]Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein
[6]Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody
[3]MERS-CoV spike protein: a key target for antivirals
[8]Advances in MERS-CoV vaccines and therapeutics based on the receptor-binding domain