ANTI-SARS-CoV-2 SPIKE (S) ANTIBODIES AND THEIR USE IN TREATING COVID-19

1 . An antibody or fragment thereof that binds to a sudden acute respiratory syndrome coronavirus 2 (CoV) Spike (S) glycoprotein, wherein the antibody or fragment thereof comprises:

(i) a variable light chain complementarity-determining region 1 (VL CDR1) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 9, 12, 15, and 18;

(ii) a variable light chain complementarity-determining region 2 (VL CDR2) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 10, 13, 16, and 19;

(iii) a variable light chain complementarity-determining region 3 (VL CDR3) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 11, 14, 17, and 20;

(iv) a variable heavy chain complementarity-determining region 1 (VH CDR1) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 21, 24, 27, and 30;

(v) a variable heavy chain complementarity-determining region 2 (VH CDR2) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 22, 25, 28, and 31; and

(vi) a variable heavy chain complementarity-determining region 3 (VH CDR3) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 23, 26, 29, and 32.

2 . An antibody or fragment thereof that binds to a sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein, wherein the antibody or fragment thereof comprises:

(i) a variable heavy (VH) domain comprising an amino acid sequence with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a polypeptide of any one of SEQ ID NOS: 5-8; and

(ii) a variable light (VL) domain comprising an amino acid sequence with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a polypeptide of any one of SEQ ID NOS: 1-4.

3 . The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises:

(i) a variable heavy (VH) domain comprising an amino acid sequence with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a polypeptide of any one of SEQ ID NOS: 5-8; and

(ii) a variable light (VL) domain comprising an amino acid sequence with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a polypeptide of any one of SEQ ID NOS: 1-4.

4 . The antibody or fragment thereof of claim 2 , wherein the antibody or fragment thereof comprises:

((i) a variable light chain complementarity-determining region 1 (VL CDR1) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 9, 12, 15, and 18;

(ii) a variable light chain complementarity-determining region 2 (VL CDR2) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 10, 13, 16, and 19;

(iii) a variable light chain complementarity-determining region 3 (VL CDR3) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 11, 14, 17, and 20;

(iv) a variable heavy chain complementarity-determining region 1 (VH CDR1) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 21, 24, 27, and 30;

(v) a variable heavy chain complementarity-determining region 2 (VH CDR2) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 22, 25, 28, and 31; and

(vi) a variable heavy chain complementarity-determining region 3 (VH CDR3) with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 23, 26, 29, and 32.

5 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof is selected from the group consisting of: a VH CDR1 according to any one of SEQ ID NOS: 21, 24, 27, and 30; a VH CDR2 according to any one of SEQ ID NO: 22, 25, 28, and 31; a VH CDR3 according to any one of SEQ ID NOS: 23, 26, 29, and 32; a VL CDR1 according to any one of SEQ ID NOS: 9, 12, 15, and 18; a VL CDR2 according to any one of SEQ ID NOS: 10, 13, 16, and 19; and a VL CDR3 according to any one of SEQ ID NOS: 11, 14, 17, and 20.

6 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof is selected from the group consisting of:

(i) a VH comprising the amino acid sequence of any one of SEQ ID NOS:5-8; and

(ii) a VL comprising the amino acid sequence of any one of SEQ ID NOS: 1-4.

7 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof is a monoclonal antibody, a Fab, F(ab′)2, Fab′, a scFv, or a single domain antibody (sdAb).

8 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof comprises a IgG1 or IgG4 domain.

9 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof has an equilibrium dissociation constant (K D ) for a CoV S glycoprotein or variant thereof of 50 nM or less, 10 nM or less, 1 nM or less, 0.5 nM or less, 0.1 nM or less, 0.05 nM or less, 0.01 nM or less, or 0.001 nM or less.

10 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof binds to a CoV S glycoprotein or variant thereof with an equilibrium dissociation constant (Kd) of less than 1.0×10 −9 moles per liter (M), less than 1.0×10 −10 M, less than 1.0×10 −11 M, or less than 1.0×10 −12 M.

11 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof binds to one or more CoV S polypeptides with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a polypeptide according to any one of SEQ ID NOS: 65-72.

12 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof is a broadly neutralizing antibody.

13 . The antibody or fragment thereof of claim 4 , wherein the antibody or fragment thereof binds to an epitope on a CoV S glycoprotein.

14 . A pharmaceutical composition, comprising an antibody or fragment thereof of claim 4 and a pharmaceutically-acceptable carrier.

15 . A method of treating a subject in need thereof infected with a SARS-CoV-2 virus or variant thereof comprising administering to the subject an antibody or fragment thereof according to claim 4 or the pharmaceutical composition of claim 14 .

16 . A method of determining if a sample contains a SARS-CoV-2 Spike (S) glycoprotein:

(a) exposing the sample to an antibody or fragment of claim 4 ;

(b) detecting the antibody or fragment thereof in the biological sample;

wherein the sample contains the SARS-CoV-2 S glycoprotein if the antibody or fragment thereof is detected in the sample.

17 . The method of claim 16 , comprising washing the sample between steps (a) and (b).

18 . The method of claim 16 , wherein detecting the antibody or fragment thereof in the sample comprises:

(i) exposing the sample to a secondary antibody; and

(ii) detecting the secondary antibody;

wherein the secondary antibody binds to the antibody or fragment of claim 4 .

19 . The method of claim 16 , wherein the sample is serum, plasma, blood, saliva, a nasopharyngeal swab, or mucus.

20 . The method of claim 16 , wherein the sample is a composition comprising a SARS-CoV-2 S glycoprotein.