Table 1 Summary of SARS-CoV-2 antibodies

RBD class 1

Neutralizing antibodies encoded by the VH3-53 gene segment, with short CDRH3 loops that block ACE2 and bind only to up RBDs.

RBS-A

Antibodies are encoded by germline genes IGHV3-53 and IGHV3-66. Similar to the ACE2-binding site, the RBS-A epitope is accessible only when the RBD is in the up conformation.

RBD-1

Contains hACE2-derived molecules and IgGs that largely overlap with the RBM.

P5A-3C8

7CHP

IGHV3-53

IGKV1-9

¹⁰⁹

RBD-2a

Bind toward the inner face of the RBD, and its binding area overlaps highly with that of the therapeutic antibody REGN10933.

REGN10933 (Casirivimab)

6XDG

IGHV3-11

IGKV1D-33

¹⁰⁸

CC12.1

6XC2

IGHV3-53

IGKV1-9

¹¹¹

CC12.3

6XC4

IGHV3-53

IGKV3-20

¹¹¹

CV30

6XE1

IGHV3-53

IGKV3-20

¹⁷⁶

COVA2-04

7JMO

IGHV3-53

IGKV3-20

⁸¹

C102

7K8M

IGHV3-53

IGKV3-20

¹⁰⁶

B38

7BZ5

IGHV3-66

IGKV1-9

¹⁷⁷

CB6 (LY-CoV016; Etesevimab)

7C01

IGHV3-66

IGKV1-39

⁸⁰

C105

6XCM

IGHV3-53

IGLV2-8

¹¹⁰

P2C-1F11 (BRII-196)

7CDI

IGHV3-66

IGKV3-20

⁹⁵

COV2-2196 (Tixagevimab)

n/a

IGHV1-58

IGKV3-20

¹⁷⁸

RBD-2b.3

Bind to the peak of the RBD, similar to antibody S2E12.

S2E12

7K4N

IGHV1-58

IGKV3-20

¹⁷⁹

RBD class 2

ACE2-blocking neutralizing antibodies that bind both up and down RBDs and can contact adjacent RBDs, including a VH3-53 antibody that uses a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation.

RBS-B

Antibodies bind at a different angle and straddle the RBS ridge, where RBD Phe486 inserts into a pocket between the light and heavy chains of the Fab on the paratope surface.

RBD-2b.1

Bind toward the outer face of the RBD, similar to antibody COVA2-39.

COVA2-39

7JMP

IGHV3-53

IGLV2-23

¹⁸⁰

CV07-250

6XKQ

IGHV1-18

IGLV2-8

¹⁸¹

BD23

7BYR

IGHV7-4-1

IGKV1-5

¹¹⁶

CT-P59 (Regdanvimab)

7CM4

IGHV2-70

IGLV1-51

¹⁸²

2-4

6XEY

IGHV1-2

IGLV2-8

¹⁸³

RBS-C

These antibodies target the back side of the RBS on the opposite side of the RBS ridge, at a different angle of approach from those that target RBS-A and RBS-B. These antibodies have fewer clashes with ACE2 binding to the RBD and can bind both up and down RBD conformations.

RBD-2b.2

Bind toward the outer face of the RBD, similar to antibody C144.

C144

7K90

IGHV3-53

IGLV2-14

¹⁰⁶

LY-CoV555 (Bamlanivimab)

7KMG

IGHV1-69

IGKV1-39

¹¹²

C121

7K8X

IGHV1-2

IGLV2-23

¹⁰⁶

RBD-4

Bind toward the outer edge of the RBM and can block ACE2, bind up and down RBD, similar to antibody C002.

BD-368-2

7CHC

IGHV3-23

IGKV2-28

¹⁸⁴

P2B-2F6

7BWJ

IGHV4-38-2

IGLV2-8

⁷⁹

CV07-270

6XKP

IGHV3-11

IGLV2-14

¹⁸¹

C002

7K8S

IGVH3-30

IGVK1-39

¹⁰⁶

C104

7K8U

IGHV1-46

IGLV2-14

¹⁰⁶

C119

7K8W

IGHV4-34

IGKV3-20

¹⁰⁶

SARS2-38

7MKM

IGHV2-9

IGKV5-44

¹⁸⁵

COV2-2130 (Cilgavimab)

n/a

IGHV3-15

IGKV4-1

¹⁷⁸

RBD class 3

Neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs.

RBS-D

RBD-5

Bind away from the RBM, toward the S309 site, and do not block ACE2. Bind up and down RBD, similar to REGN10987. Inter-spike cross-linking.

REGN10987 (Imdevimab)

6XDG

IGHV3-30

IGLV2-14

¹⁰⁸

C110

7K8V

IGVH5-51

IGVK1-5

¹⁰⁶

C135

7K8Z

IGHV3-30

IGKV1-5

¹⁰⁶

LY-CoV1404 (Bebtelovimab)

7MMO

IGHV2-5

IGLV2-14

¹²⁶

BRII-198

n/a

n/a

n/a

¹⁰²

S309 proteoglycan

Bind N343 glycan and can bind in up and down RBD.

S309 (Sotrovimab)

6WPS

IGHV1-18

IGKV3-20

⁴⁷

RBD class 4

Do not block ACE2 and bind only to up RBDs.

CR3022 cryptic

CR3022 site has been found to be a target of cross-neutralizing antibodies against SARS-CoV-2.

RBD-3

Bind down from the center of the ACE2 binding site toward the RBD mesa, similar to antibody ADI-56046.

ADI-56046

n/a

n/a

n/a

¹⁸⁶

RBD-6

Bind to the inner face of the RBD and require two RBDs to be in the up configuration. Block ACE2 and compete with RBD-2a antibodies.

COVA1-16

7JMW

IGHV1-46

IGKV1D-33

¹⁸⁷

DH1047

7LD1

IGHV1-46

IGKV4-1

¹⁸⁸

RBD-7

Bind to the inner face of the RBD and require two RBDs to be in the up configuration. Downward shift of the RBD-7 footprint allows simultaneous binding of RBD-2a antibodies with RBD-7.

CR3022

6W41

IGHV5-51

IGKV4-1

¹⁸⁹

EY6A

6ZCZ

IGHV3-30-3

IGKV1-39

¹⁹⁰

H014

7CAI

IGHV1-69-2

IGKV6-21

¹⁹¹

S2X259

7RA8

IGHV1-69

IGLV1-40

¹²⁹

NTD

NTD-1

Bind from the top side of the NTD to cover the NTD N terminus and residue Y144. Epitope overlaps with that of monoclonal antibody 4A8 and other ‘supersite’ binders.

4A8

7C2L

IGHV1-24

IGKV2-24

¹²⁸

4-8

7LQV

IGHV1-69

IGLV3-1

¹⁸³