A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

doi:10.1016/j.chom.2021.04.005

. 2021 May 12;29(5):806-818.e6.

doi: 10.1016/j.chom.2021.04.005. Epub 2021 Apr 15.

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Hejun Liu¹, Meng Yuan¹, Deli Huang², Sandhya Bangaru¹, Fangzhu Zhao², Chang-Chun D Lee¹, Linghang Peng², Shawn Barman², Xueyong Zhu¹, David Nemazee², Dennis R Burton³, Marit J van Gils⁴, Rogier W Sanders⁵, Hans-Christian Kornau⁶, S Momsen Reincke⁷, Harald Prüss⁷, Jakob Kreye⁸, Nicholas C Wu⁹, Andrew B Ward¹, Ian A Wilson¹⁰

Affiliations

¹ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
² Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
⁴ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
⁶ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁷ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Helmholtz Innovation Lab BaoBab, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁸ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Helmholtz Innovation Lab BaoBab, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁹ Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
¹⁰ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu.

PMID: 33894127
PMCID: PMC8049401
DOI: 10.1016/j.chom.2021.04.005

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Hejun Liu et al. Cell Host Microbe. 2021.

. 2021 May 12;29(5):806-818.e6.

doi: 10.1016/j.chom.2021.04.005. Epub 2021 Apr 15.

Authors

Affiliations

¹ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
² Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
⁴ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
⁶ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Neuroscience Research Center (NWFZ), Cluster NeuroCure, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁷ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Helmholtz Innovation Lab BaoBab, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁸ German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Helmholtz Innovation Lab BaoBab, Berlin, Germany; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
⁹ Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
¹⁰ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu.

PMID: 33894127
PMCID: PMC8049401
DOI: 10.1016/j.chom.2021.04.005

Abstract

Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

Keywords: 3D structure; COVID-19; SARS-CoV-2; antibody cocktail; antibody-antigen interaction; coronavirus; cross-neutralizing antibody; crystallography; synergy.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests A patent application for SARS-CoV-2 antibody CV38-142 was first disclosed in (Kreye et al., 2020) and filed under application number 20182069.3 by some of the authors at Neurodegenerative Diseases (DZNE) and Charité-Universitätsmedizin Berlin. The Amsterdam UMC filed a patent on SARS-CoV-2 antibodies including COVA1-16 under application number 2020-039EP-PR that included the AMC authors on this paper.

Figures

**Figure 1**
CV38-142 binds and cross-neutralizes SARS-CoV-2 and SARS-CoV (A) CV38-142 Fab binds to RBDs from human, bat, and pangolin sarbecoviruses with generally similar affinities. Binding kinetics were measured by biolayer interferometry (BLI) with RBDs on the biosensor and Fab in solution. Concentrations of Fab serial dilution are shown in the inset in the lower right panel. The association and disassociation were recorded in real time (s) on the x axis with binding response (nm) on the y axis with colored lines. Disassociation constant (K_D) values were obtained by fitting a 1:1 binding model. The fitted curves are represented by the dashed lines (black). (B) CV38-142 neutralizes both SARS-CoV-2 and SARS-CoV, while its Fab counterpart barely neutralizes the two pseudotype viruses at the highest concentrations tested in the same neutralization assay. The IgG half-maximal inhibitory concentration (IC₅₀) values (3.46 μg/mL for SARS-CoV-2 and 1.41 μg/mL for SARS-CoV) were determined using Prism software (version 8.4.3). Error bars indicate standard deviation (SD) of at least two biological replicates.

**Figure 2**
CV38-142 can be combined with antibodies to the receptor binding site or CR3022 cryptic site (A) Competitive binding of CV38-142 to SARS-CoV-2 RBD or spike. Inset in the right panel shows a zoomed-in view for Fabs/ACE2 binding on spike. A sandwich binding assay was used for the competition assay. CV38-142 IgG was first pre-loaded on the biosensor, then SARS-CoV-2 RBD or spike was loaded at the indicated time point. The biosensors with captured antibody-antigen complex were tested against binding to a second antibody Fab or human ACE2. Loading events for RBD/spike and the second antibody Fab/ACE2 are indicated by arrows along the timeline (x axis), while the binding response (nm, y axis) was recorded in real time as colored lines corresponding to each antibody Fab or ACE2. (B) Cross-neutralization dose-response matrix of an antibody cocktail consisting of CV38-142 and COVA1-16. The pseudovirus neutralization assay was performed by addition of mixtures of varying ratios of CV38-142 and COVA1-16. The percentage neutralization for each experiment with SARS-CoV-2 and SARS-CoV is plotted on heatmap matrices with their corresponding color bar shown on the right. See also Figure S1.

**Figure 3**
The CV38-142 epitope on the RBD involves an N-glycosylation site on SARS-CoV-2 and SARS-CoV (A) Ribbon representation of the crystal structures of SARS-CoV-2 (left) and SARS-CoV (middle) RBD in complex with CV38-142 Fab and comparison to cryo-EM structure of S309 Fab in complex with spike trimer (PDB: 6WPS) (right, only the comparable RBD regions are shown). CV38-142 Fab heavy chain is in forest green and light chain in wheat, S309 Fab heavy chain in gray and light chain in cyan, SARS-CoV-2 RBD in white, and SARS-CoV RBD in pale blue. The N343 glycan in SARS-CoV-2 and N330 glycan in SARS-CoV are shown as sticks. The same perspective views are used for the comparison. The overall structure of SARS-CoV-2 RBD in complex with CV38-142 and COVA1-16 is shown in Figure S1A. (B) Interactions between CV38-142 Fab residues and N343 (SARS-CoV-2) and N330 (SARS-CoV) glycans are shown in stick representation. Water molecules mediating the antibody-antigen interaction are shown in spheres (gray; yellow for shared water-mediated interactions between SARS-CoV-2 and SARS-CoV). Dashed lines (black) represent hydrogen bonds. Residues of the heavy and light chain are both involved in the interactions with glycans. The interactions of CV38-142 with SARS-CoV-2 RBD and SARS-CoV RBD are similar. (C) Glycan removal in the RBD decreases binding between CV38-142 and SARS-CoV-2 RBD. The binding kinetics were measured by BLI with CV38-142 Fab on the biosensor and RBD in solution. SARS-CoV-2 RBD was pretreated with or without PNGase F digestion in the same concentration and condition before being used in the BLI assay. Concentrations of RBD serial dilution are shown in the right panel. The association and disassociation were recorded in real time (s) in the x axis and response (nm) on the y axis as colored lines. Disassociation constant (K_D) values were obtained by fitting a 1:1 binding model with fitted curves represented by the dash lines. See also Figure S2 and Table S1.

**Figure 4**
Molecular interactions between CV38-142 and RBDs SARS-CoV-2 RBD is in white, SARS-CoV RBD in pale blue, CV38-142 heavy chain in forest green and light chain in wheat, and ACE2 in pale green. Corresponding residues that differ between SARS-CoV-2 and SARS-CoV are labeled with asterisks (^∗). Dashed lines (black) represent hydrogen bonds or salt bridges. (A) Direct interactions between CV38-142 and SARS-CoV-2 RBD are shown in sticks. (B) Surface representation of the CV38-142 epitope site in SARS-CoV-2 RBD. The CV38-142 epitope is exposed to solvent regardless of whether the RBD is in the “up” or “down” state. RBDs are shown in surface representation model with symmetry derived from the spike protein (PDB: 6VYB) to show their solvent-accessible surface area in either “up” or “down” state. The buried surface area (BSA) was calculated by PISA program (Krissinel and Henrick, 2007). The epitope surface buried by the CV38-142 heavy chain is shown in orange and that by the light chain in purple. The total surface area buried on the RBD by CV38-142 is 792 Å² with 629 Å² (79%) contributed by the heavy chain and 163 Å² (21%) by the light chain. (C) Direct interactions between CV38-142 and SARS-CoV RBD. The same perspective is used as in (A). (D) Structural alignment illustrating a model with simultaneous binding by CV38-142 and ACE2 to SARS-CoV-2 RBD. Structures of CV38-142 Fab + SARS-CoV-2 RBD and ACE2 + SARS-CoV-2 spike are aligned by superimposition of their RBD. The scale bar shows the closest distance between ACE2 and CV38-142, which is 6 Å, although some sugars in the N53 glycan are not visible in the electron density map. See also Figures S3 and S5 and Table S2.

**Figure 5**
A plethora of water molecules mediate interactions between CV38-142 and SARS-CoV-2 and SARS-CoV RBD SARS-CoV-2 RBD is in white, SARS-CoV RBD in pale blue, CV38-142 heavy chain in forest green and light chain in wheat. Corresponding residues that differ between SARS-CoV-2 and SARS-CoV are labeled with asterisks (^∗). Dashed lines (black) represent hydrogen bonds. Amino acid residues as well as the glycans involved in the water-mediated interactions are shown in sticks. Yellow spheres indicate water molecules in the same location in the structures of the CV38-142 Fab + SARS-CoV-2 RBD + COVA1-16 Fab complex (A) and the CV38-142 Fab + SARS-CoV RBD (B). Grey spheres indicate unique water molecules in each complex structure. See also Figure S4.

**Figure 6**
CV38-142 Fab binding to SARS-CoV-2 and SARS-CoV spike trimers by nsEM (A) CV38-142 Fab binding to spike trimers as observed by nsEM. Representative 3D nsEM reconstructions are shown of CV38-142 Fab complexed with the spike trimers with its RBDs in “up” and “down” states. The location of the bound CV38-142 Fabs are indicated by arrow heads. SARS-CoV-2 (pink) or SARS-CoV (yellow) spikes with at least one “up” RBD and one “down” RBD are bound by two CV38-142 Fabs. The spikes (pale blue to SARS-CoV-2 and gray to SARS-CoV) with RBD in the two “down,” one “up” states are bound by three Fabs. Other binding stoichiometries and conformations are show in Figure S6. (B–D) C-terminal distances of CV38-142 Fab binding to spikes. The three RBDs (B) or three protomers (C and D) in the spike trimer are shown in white, gray, and dark gray, respectively. CV38-142 Fabs are shown in ribbon representation with heavy chain in forest green and light chain in wheat. The C termini of CV38-142 heavy chains are shown as spheres (yellow). Dashed lines represent distances among the various combinations of C-termini. (B) nsEM fitting model. To measure the distances between C-termini of CV38-142 Fabs in nsEM data, the crystal structure of CV38-142 Fab + SARS-CoV-2 was fitted into the nsEM density in (A) (second from the left). (C and D) Structural superimposition of CV38-142 Fabs onto the spike trimer, which is shown in surface representation. Alignment of CV38-142 Fab binding to the spike trimer with RBD in two “up,” one “down” state (PDB: 7CAI) (C) or to a dimeric spike trimer that is found in Novavax vaccine candidate NVAX-CoV2373 with RBD in “all-down” state (PDB: 7JJJ) (Bangaru et al., 2020) (D). The (B–D) models represent various possibilities of CV38-142 binding to the spike protein on the viral surface. See also Figure S6.

**Figure 7**
A combination of CV38-142 and COVA1-16 neutralizes circulating SARS-CoV-2 variants of concern Individual antibodies CV38-142, COVA1-16, and a mixture in a 1:1 molar ratio, were tested in a pseudovirus assay. CV38-142 showed similar potency (upper right panel) on neutralizing wild-type (Wuhan-Hu-1) SARS-CoV-2 pseudovirus (upper left panel) and two circulating variants of concern, i.e., B.1.1.7 isolated in the UK (lower left panel) and B.1.351 isolated in South Africa, namely 501Y.V2 (lower right panel). Although COVA1-16 showed a slight decrease in neutralization potency against B.1.1.7 and B.1.351, the combinatorial use of the two antibodies showed enhanced neutralization against all three viruses (upper right panel). Error bars indicate standard deviation (SD) of at least two biological replicates.

See this image and copyright information in PMC

Update of

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection.
Liu H, Yuan M, Huang D, Bangaru S, Lee CD, Peng L, Zhu X, Nemazee D, van Gils MJ, Sanders RW, Kornau HC, Reincke SM, Prüss H, Kreye J, Wu NC, Ward AB, Wilson IA. Liu H, et al. bioRxiv [Preprint]. 2021 Feb 12:2021.02.11.430866. doi: 10.1101/2021.02.11.430866. bioRxiv. 2021. Update in: Cell Host Microbe. 2021 May 12;29(5):806-818.e6. doi: 10.1016/j.chom.2021.04.005 PMID: 33594361 Free PMC article. Updated. Preprint.

Cited by

Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern.
Kovacech B, Fialova L, Filipcik P, Skrabana R, Zilkova M, Paulenka-Ivanovova N, Kovac A, Palova D, Rolkova GP, Tomkova K, Csokova NT, Markova K, Skrabanova M, Sinska K, Basheer N, Majerova P, Hanes J, Parrak V, Prcina M, Cehlar O, Cente M, Piestansky J, Fresser M, Novak M, Slavikova M, Borsova K, Cabanova V, Brejova B, Vinař T, Nosek J, Klempa B, Eyer L, Hönig V, Palus M, Ruzek D, Vyhlidalova T, Strakova P, Mrazkova B, Zudova D, Koubkova G, Novosadova V, Prochazka J, Sedlacek R, Zilka N, Kontsekova E. Kovacech B, et al. EBioMedicine. 2022 Feb;76:103818. doi: 10.1016/j.ebiom.2022.103818. Epub 2022 Jan 22. EBioMedicine. 2022. PMID: 35078012 Free PMC article.
Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies.
Jette CA, Cohen AA, Gnanapragasam PNP, Muecksch F, Lee YE, Huey-Tubman KE, Schmidt F, Hatziioannou T, Bieniasz PD, Nussenzweig MC, West AP Jr, Keeffe JR, Bjorkman PJ, Barnes CO. Jette CA, et al. Cell Rep. 2021 Sep 28;36(13):109760. doi: 10.1016/j.celrep.2021.109760. Epub 2021 Sep 8. Cell Rep. 2021. PMID: 34534459 Free PMC article.
Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses.
Radić L, Sliepen K, Yin V, Brinkkemper M, Capella-Pujol J, Schriek AI, Torres JL, Bangaru S, Burger JA, Poniman M, Bontjer I, Bouhuijs JH, Gideonse D, Eggink D, Ward AB, Heck AJR, Van Gils MJ, Sanders RW, Schinkel J. Radić L, et al. iScience. 2023 Apr 21;26(4):106540. doi: 10.1016/j.isci.2023.106540. Epub 2023 Mar 31. iScience. 2023. PMID: 37063468 Free PMC article.
Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines.
García-Vega M, Wan H, Reséndiz-Sandoval M, Hinojosa-Trujillo D, Valenzuela O, Mata-Haro V, Dehesa-Canseco F, Solís-Hernández M, Marcotte H, Pan-Hammarström Q, Hernández J. García-Vega M, et al. Genes Immun. 2024 Apr;25(2):158-167. doi: 10.1038/s41435-024-00270-x. Epub 2024 Apr 3. Genes Immun. 2024. PMID: 38570727
Monoclonal antibody therapies in the management of SARS-CoV-2 infection.
Miguez-Rey E, Choi D, Kim S, Yoon S, Săndulescu O. Miguez-Rey E, et al. Expert Opin Investig Drugs. 2022 Jan;31(1):41-58. doi: 10.1080/13543784.2022.2030310. Epub 2022 Feb 14. Expert Opin Investig Drugs. 2022. PMID: 35164631 Free PMC article.

See all "Cited by" articles

References

1. Adams P.D., Afonine P.V., Bunkóczi G., Chen V.B., Davis I.W., Echols N., Headd J.J., Hung L.-W., Kapral G.J., Grosse-Kunstleve R.W. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 2010;66:213–221. - PMC - PubMed
1. Andreano E., Piccini G., Licastro D., Casalino L., Johnson N.V., Paciello I., Monego S.D., Pantano E., Manganaro N., Manenti A. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. bioRxiv. 2020 doi: 10.1101/2020.12.28.424451. 2020.12.28.424451. - DOI - PMC - PubMed
1. Bangaru S., Ozorowski G., Turner H.L., Antanasijevic A., Huang D., Wang X., Torres J.L., Diedrich J.K., Tian J.H., Portnoff A.D. Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Science. 2020;370:1089–1094. - PMC - PubMed
1. Barnes C.O., Jette C.A., Abernathy M.E., Dam K.A., Esswein S.R., Gristick H.B., Malyutin A.G., Sharaf N.G., Huey-Tubman K.E., Lee Y.E. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020;588:682–687. - PMC - PubMed
1. Barnes C.O., West A.P., Jr., Huey-Tubman K.E., Hoffmann M.A.G., Sharaf N.G., Hoffman P.R., Koranda N., Gristick H.B., Gaebler C., Muecksch F. Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. Cell. 2020;182:828–842.e16. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
Medical
- MedlinePlus Health Information
Research Materials
- Addgene Non-profit plasmid repository
Miscellaneous
- NCI CPTAC Assay Portal

[1] Adams P.D., Afonine P.V., Bunkóczi G., Chen V.B., Davis I.W., Echols N., Headd J.J., Hung L.-W., Kapral G.J., Grosse-Kunstleve R.W. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 2010;66:213–221. - PMC - PubMed

[2] Adams P.D., Afonine P.V., Bunkóczi G., Chen V.B., Davis I.W., Echols N., Headd J.J., Hung L.-W., Kapral G.J., Grosse-Kunstleve R.W. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 2010;66:213–221. - PMC - PubMed

[3] Andreano E., Piccini G., Licastro D., Casalino L., Johnson N.V., Paciello I., Monego S.D., Pantano E., Manganaro N., Manenti A. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. bioRxiv. 2020 doi: 10.1101/2020.12.28.424451. 2020.12.28.424451. - DOI - PMC - PubMed

[4] Andreano E., Piccini G., Licastro D., Casalino L., Johnson N.V., Paciello I., Monego S.D., Pantano E., Manganaro N., Manenti A. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. bioRxiv. 2020 doi: 10.1101/2020.12.28.424451. 2020.12.28.424451. - DOI - PMC - PubMed

[5] Bangaru S., Ozorowski G., Turner H.L., Antanasijevic A., Huang D., Wang X., Torres J.L., Diedrich J.K., Tian J.H., Portnoff A.D. Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Science. 2020;370:1089–1094. - PMC - PubMed

[6] Bangaru S., Ozorowski G., Turner H.L., Antanasijevic A., Huang D., Wang X., Torres J.L., Diedrich J.K., Tian J.H., Portnoff A.D. Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Science. 2020;370:1089–1094. - PMC - PubMed

[7] Barnes C.O., Jette C.A., Abernathy M.E., Dam K.A., Esswein S.R., Gristick H.B., Malyutin A.G., Sharaf N.G., Huey-Tubman K.E., Lee Y.E. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020;588:682–687. - PMC - PubMed

[8] Barnes C.O., Jette C.A., Abernathy M.E., Dam K.A., Esswein S.R., Gristick H.B., Malyutin A.G., Sharaf N.G., Huey-Tubman K.E., Lee Y.E. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020;588:682–687. - PMC - PubMed

[9] Barnes C.O., West A.P., Jr., Huey-Tubman K.E., Hoffmann M.A.G., Sharaf N.G., Hoffman P.R., Koranda N., Gristick H.B., Gaebler C., Muecksch F. Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. Cell. 2020;182:828–842.e16. - PMC - PubMed

[10] Barnes C.O., West A.P., Jr., Huey-Tubman K.E., Hoffmann M.A.G., Sharaf N.G., Hoffman P.R., Koranda N., Gristick H.B., Gaebler C., Muecksch F. Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. Cell. 2020;182:828–842.e16. - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Affiliations

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Update of

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous

Abstract

Conflict of interest statement

Figures

Update of

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous