The antigenic anatomy of SARS-CoV-2 receptor binding domain
Open accessAbstract
Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC 50 < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.
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The affinity of B.1.351 RBD for soluble ACE2 is 19-fold higher than for Victoria RBD and 2.7-fold higher than for B.1.1.7 RBD.
“As expected, the affinity for B.1.351 RBD is high; in fact, it is 19-fold higher than for the Victoria RBD and 2.7-fold higher than for B.1.1.7 ((Dejnirattisai et al., 2021); Supasa et al., 2021).”
From Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera (2021) · cites this paper as Dejnirattisai et al., 2021
For Fabs tested against B.1.351, only 4 (or 2 if engineered LC versions of 253 are removed) had KDs below 4 nM, compared with 17 against Victoria, and 7 Fabs failed to achieve near-micromolar affinity.
“whereas for the antigen binding fragments (Fabs) tested against Victoria, 17 had KDs below 4 nM (the affinity of ACE2 for B.1.351) against B.1.351, this reduced to 4 (or 2 if the engineered light-chain [LC] versions of 253 are removed [(Dejnirattisai et al., 2021)]), with 7 Fabs failing to achieve near-micromolar affinity.”
From Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera (2021) · cites this paper as Dejnirattisai et al., 2021
There was a correlation between ACE2 blocking and neutralization titers.
“As expected, there was a correlation between ACE2 blocking and neutralization titers”
From Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera (2021) · cites this paper as Dejnirattisai et al., 2021
B.1.1.7 showed only a 5.7-fold reduction in FRNT50 for mAb 159 (Victoria 11 ng/mL, B.1.1.7 61 ng/mL), suggesting that despite the residue 144 deletion being on the edge of the antibody footprint, the binding site has not been completely disrupted.
“In this study, B.1.1.7 showed only a 5.7-fold reduction in the FRNT50 for mAb 159 (FRNT50 Victoria 11 ng/mL B.1.1.7 61 ng/mL) suggesting that despite the residue 144 deletion being on the edge of the footprint for this antibody (Dejnirattisai et al., 2021) the binding site has not been completely disrupted.”
From Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera (2021) · cites this paper as Dejnirattisai et al., 2021
In the prior study, all 20 potent neutralizing antibodies (FRNT50 <0.1 μg/mL for Victoria) bound the RBD, except mAb 159, which bound the NTD.
“In that study, neutralization titers established that all 20 potent neutralizing antibodies (FRNT50 <0.1 μg/mL for the Victoria virus) bound the RBD, with the single exception of mAb 159, which bound the NTD.”
From Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera (2021) · cites this paper as Dejnirattisai et al., 2021
Mutations K417T, E484K, and N501Y in the ACE2 interacting surface are of greatest concern because of their potential to promote escape from the neutralizing antibody response, which predominately targets this region.
“Mutations K417T, E484K, and N501Y in the ACE2 interacting surface are of the greatest concern because of their potential to promote escape from the neutralizing antibody response, which predominately targets this region”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
Residue 188 is somewhat occluded, whereas residue 20 is highly exposed, close to the site of attachment of neutralizing antibody 159, and impinges on the proposed NTD supersite.
“Residue 188 is somewhat occluded, whereas residue 20 is highly exposed, is close to the site of attachment of neutralizing antibody 159 (Dejnirattisai et al., 2021), and impinges on the proposed NTD supersite.”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
Structures of mAbs 150, 158, and 269 show no contacts with residue 484, interactions of CDR-H3 with K417 and CDR-L1 with N501, meaning binding and neutralization by VH3-53 antibodies would be predicted to be compromised by N501Y, while the additional change at 417 might have an additive effect.
“while there are no contacts with residue 484, there are interactions of CDR-H3 with K417 and CDR-L1 with N501, meaning that binding and neutralization by VH3–53 antibodies would be predicted to be compromised by the N501Y change in variant viruses B.1.1.7, B.1.351, and P.1, while the additional change at 417 in P.1 (K417T) and B.1.351 (K417N) might be expected to have an additive effect”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
The NTD mutations in P.1 (L18F, T20N, P26S, D138Y, and R190S) disrupt the epitope for mAb159.
“it is clear that the NTD mutations in P.1 (L18F, T20N, P26S, D138Y, and R190S) disrupt the epitope for mAb159”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
VH3-53 antibody engagement with the RBD is dictated by CDR-H1 and CDR-H2, while the CDR-H3 is characteristically short and makes rather few interactions.
“Their engagement with the RBD is dictated by CDR-H1 and CDR-H2, while the CDR-H3 is characteristically short and makes rather few interactions”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
Public antibody responses for SARS-CoV-2 include principally VH3-53/VH3-66 and VH1-58, with VH3-30 also found but not potent neutralizers.
“A number of public antibody responses have been reported for SARS-CoV-2, principal among these being VH3–53/VH3–66 and VH1–58 (VH3–30 is also found, but the antibodies are not potent neutralizers) (Yuan et al., 2020; Barnes et al., 2020; Dejnirattisai et al., 2021).”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
Comparison of pseudoviruses expressing only the three RBD mutations of B.1.351 with pseudovirus expressing the full suite of B.1.351 spike mutations shows that non-RBD changes substantially increase escape from neutralization.
“Comparison of neutralization of pseudoviruses expressing only the three RBD mutations (K417N, E484K, and N501Y) of B.1.351 with pseudovirus expressing the full suite of mutations in B.1.351 spike shows that the non-RBD changes substantially increase escape from neutralization (Wibmer et al., 2021; Dejnirattisai et al., 2021; Wang et al., 2021).”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
Mixing heavy and light chains from antibodies within VH1-58 can increase neutralization titer by 20-fold from parent antibodies.
“We have previously shown that mixing heavy and light chains from antibodies within VH1–58 can increase the neutralization titer by 20-fold from the parent antibodies (chimera of 253HC with 55LC or 165LC) (Dejnirattisai et al., 2021).”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
Structures of WT RBD-EY6A-222 and the P.1 RBD-ACE2 complexes were determined by molecular replacement with PHASER using search models of SARS-CoV-2 RBD-EY6A-H4 (PDB ID 6ZCZ), RBD-158 (PDB ID 7BEK), and a RBD and ACE2 complex (PDB ID 6LZG).
“Structures of WT RBD-EY6A-222 and the P.1 RBD-ACE2 complexes were determined by molecular replacement with PHASER (McCoy et al., 2007) using search models of SARS-CoV-2 RBD-EY6A-H4 (PDB ID 6ZCZ) (Zhou et al., 2020) and RBD-158 (PDB ID, 7BEK) (Dejnirattisai et al., 2021) complexes, and a RBD and ACE2 complex (PDB ID, 6LZG; Wang et al., 2020), respectively.”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
The constructs of EY6A Fab, 222 Fab, ACE2, WT RBD, B.1.1.7 and B.1.351 mutant RBD are the same as previously described.
“The constructs of EY6A Fab, 222 Fab, ACE2, WT RBD, B.1.1.7 and B.1.351 mutant RBD are the same as previously described (Dejnirattisai et al., 2021; Zhou et al., 2021; Supasa et al., 2021).”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Dejnirattisai et al., 2021
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Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286 · see citing works
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination
Punjani, A., Rubinstein, J. L., Fleet, D. J., & Brubaker, M. A. (2017) · Nature Methods · doi:10.1038/nmeth.4169 · Cited by 9,168 · see citing works
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897 · see citing works
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586 · see citing works
Liebschner, D. C., Afonine, P. V., Baker, M. L., Bunkòczi, G., Chen, V. B., Croll, T. I., Hintze, B. J., Hung, L., Jain, S., McCoy, A. J., et al. (2019) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319011471 · Cited by 6,709 · see citing works
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2180-5 · Cited by 5,983 · see citing works
Automated electron microscope tomography using robust prediction of specimen movements.
Mastronarde, D. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.07.007 · Cited by 5,446 · see citing works
New tools for automated high-resolution cryo-EM structure determination in RELION-3
Zivanov, J., Nakane, T., Forsberg, B., Kimanius, D., Hagen, W., Lindahl, E., & Scheres, S. (2018) · eLife · doi:10.7554/elife.42166 · Cited by 4,377 · see citing works
Gctf: Real-time CTF determination and correction
Zhang, K. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.11.003 · Cited by 3,372 · see citing works
SARS-CoV-2 vaccines in development
Krammer, F. (2020) · Nature · doi:10.1038/s41586-020-2798-3 · Cited by 2,098 · see citing works
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Pinto, D., Park, Y.-J., Beltramello, M., Walls, A. C., Tortorici, M. A., Bianchi, S., Jaconi, S., Culap, K., Zatta, F., De Marco, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2349-y · Cited by 1,885 · see citing works
Self-citationHuman neutralizing antibodies elicited by SARS-CoV-2 infection
Ju, B., Zhang, Q., Ge, J., Wang, R., Sun, J., Ge, X., Yu, J., Shan, S., Zhou, B., Song, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2380-z · Cited by 1,667 · cited 1× · see citing works
“Although the orientation of 384 is similar to a group of previously reported Fabs (CV07-270, p2b-2f6 and bd629, (Kreye et al., 2020; Ju et al., 2020; Du et al., 2020)), it is shifted 20 Å towards the left shoulder such that it does not contact the right chest ( Figures 3, 4E).”
xia2 : an expert system for macromolecular crystallography data reduction
Winter, G. (2009) · Journal of Applied Crystallography · doi:10.1107/s0021889809045701 · Cited by 1,530 · see citing works
A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV
Yuan, M., Wu, N. C., Zhu, X., Lee, C.-C. D., So, R. T. Y., Lv, H., Mok, C. K. P., & Wilson, I. A. (2020) · Science · doi:10.1126/science.abb7269 · Cited by 1,405 · see citing works
Piccoli, L., Park, Y.-J., Tortorici, M. A., Czudnochowski, N., Walls, A. C., Beltramello, M., Silacci-Fregni, C., Pinto, D., Rosen, L. E., Bowen, J. E., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.037 · Cited by 1,395 · see citing works
Self-citationA neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2
Chi, X., Yan, R., Zhang, J., Zhang, G., Zhang, Y., Hao, M., Zhang, Z., Fan, P., Dong, Y., Yang, Y., et al. (2020) · Science · doi:10.1126/science.abc6952 · Cited by 1,385 · see citing works
Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike
Liu, L., Wang, P., Nair, M. S., Yu, J., Rapp, M., Wang, Q., Luo, Y., Chan, J. F.-W., Sahi, V., Figueroa, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2571-7 · Cited by 1,349 · see citing works
A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2
Shi, R., Shan, C., Duan, X., Chen, Z., Liu, P., Song, J., Song, T., Bi, X., Han, C., Wu, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2381-y · Cited by 1,286 · see citing works
Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., et al. (2020) · Science · doi:10.1126/science.abd0831 · Cited by 1,253 · see citing works
Tian, X., Li, C., Huang, A., Xia, S., Lu, S., Shi, Z., Lu, L., Jiang, S., Yang, Z., Wu, Y., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1729069 · Cited by 1,239 · see citing works
Distinct conformational states of SARS-CoV-2 spike protein
Cai, Y., Zhang, J., Xiao, T., Peng, H., Sterling, S. M., Walsh, R. M., Rawson, S., Rits-Volloch, S., & Chen, B. (2020) · Science · doi:10.1126/science.abd4251 · Cited by 1,221 · see citing works
DIALS : implementation and evaluation of a new integration package
Winter, G., Waterman, D. G., Parkhurst, J. M., Brewster, A. S., Gildea, R. J., Gerstel, M., Fuentes‐Montero, L., Vollmar, M., Michels-Clark, T., Young, I. D., et al. (2018) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798317017235 · Cited by 1,128 · see citing works
Structures and distributions of SARS-CoV-2 spike proteins on intact virions
Ke, Z., Otón, J., Qu, K., Cortese, M., Žíla, V., McKeane, L., Nakane, T., Zivanov, J., Neufeldt, C. J., Cerikan, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2665-2 · Cited by 1,114 · see citing works
Potently neutralizing and protective human antibodies against SARS-CoV-2
Zost, S. J., Gilchuk, P., Case, J. B., Binshtein, E., Chen, R. E., Nkolola, J. P., Schäfer, A., Reidy, J. X., Trivette, A., Nargi, R. S., et al. (2020) · Nature · doi:10.1038/s41586-020-2548-6 · Cited by 1,041 · see citing works
Self-citationMcCray, P. B., Pewe, L., Wohlford-Lenane, C., Hickey, M., Manzel, L., Shi, L., Netland, J., Jia, H. P., Halabi, C., Sigmund, C. D., et al. (2007) · Journal of Virology · doi:10.1128/jvi.02012-06 · Cited by 1,010 · see citing works
Wu, Y., Wang, F., Shen, C., Peng, W., Li, D., Zhao, C., Li, Z., Li, S., Bi, Y., Yang, Y., et al. (2020) · Science · doi:10.1126/science.abc2241 · Cited by 955 · see citing works
Winkler, E. S., Bailey, A. L., Kafai, N. M., Nair, S., McCune, B. T., Yu, J., Fox, J. M., Chen, R. E., Earnest, J. T., Keeler, S. P., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0778-2 · Cited by 901 · cited 2× · see citing works
“In this model, SARS-CoV-2 infected animals develop severe pulmonary disease and high levels of viral infection in the lung that is accompanied by immune cell infiltration and tissue damage (Winkler et al., 2020).”
Self-citationBarnes, C. O., West, A. P., Huey-Tubman, K. E., Hoffmann, M. A. G., Sharaf, N. G., Hoffman, P. R., Koranda, N., Gristick, H. B., Gaebler, C., Muecksch, F., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.025 · Cited by 795 · see citing works
Yuan, Y., Cao, D., Zhang, Y., Ma, J., Qi, J., Wang, Q., Lu, G., Wu, Y., Yan, J., Shi, Y., et al. (2017) · Nature Communications · doi:10.1038/ncomms15092 · Cited by 761 · see citing works
A time- and cost-efficient system for high-level protein production in mammalian cells
Aricescu, A. R., Lu, W., & Jones, E. Y. (2006) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444906029799 · Cited by 746 · see citing works
Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis
Johnson, B. A., Xie, X., Bailey, A. L., Kalveram, B., Lokugamage, K. G., Muruato, A., Zou, J., Zhang, X., Juelich, T., Smith, J. K., et al. (2021) · Nature · doi:10.1038/s41586-021-03237-4 · Cited by 694 · see citing works
Self-citationStructural basis of a shared antibody response to SARS-CoV-2
Yuan, M., Liu, H., Wu, N. C., Lee, C.-C. D., Zhu, X., Zhao, F., Huang, D., Yu, W., Hua, Y., Tien, H., et al. (2020) · Science · doi:10.1126/science.abd2321 · Cited by 589 · see citing works
Chen, L., Liu, W., Qi, Z., Xu, K., Ye, G., Wu, W.-C., Sun, Z., Liu, F., Wu, K., Zhong, B., et al. (2020) · Emerging Microbes & Infections · doi:10.1080/22221751.2020.1725399 · Cited by 570 · see citing works
Receptor Recognition Mechanisms of Coronaviruses: a Decade of Structural Studies
Li, F. (2014) · Journal of Virology · doi:10.1128/jvi.02615-14 · Cited by 569 · see citing works
Simmons, G., Reeves, J. D., Rennekamp, A. J., Amberg, S. M., Piefer, A. J., & Bates, P. F. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306446101 · Cited by 543 · see citing works
Jaimes, J. A., André, N. M., Chappie, J. S., Millet, J. K., & Whittaker, G. R. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.04.009 · Cited by 485 · see citing works
A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies
Hassan, A. O., Case, J. B., Winkler, E. S., Thackray, L. B., Kafai, N. M., Bailey, A. L., McCune, B. T., Fox, J. M., Chen, R. E., Alsoussi, W. B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.011 · Cited by 477 · see citing works
Self-citationFree fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein
Toelzer, C., Gupta, K., Yadav, S. K. N., Borucu, U., Davidson, A. D., Williamson, M. K., Shoemark, D. K., Garzoni, F., Staufer, O., Milligan, R., et al. (2020) · Science · doi:10.1126/science.abd3255 · Cited by 419 · see citing works
Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
Lv, Z., Deng, Y., Ye, Q., Cao, L., Sun, C.-Y., Fan, C., Huang, W., Sun, S., Sun, Y., Zhu, L., et al. (2020) · Science · doi:10.1126/science.abc5881 · Cited by 362 · see citing works
Matrosovich, M. N., Matrosovich, T. Y., Carr, J., Roberts, N. A., & Klenk, H. (2003) · Journal of Virology · doi:10.1128/jvi.77.15.8418-8425.2003 · Cited by 359 · see citing works
Kreye, J., Reincke, S. M., Kornau, H.-C., Sánchez-Sendin, E., Corman, V. M., Liu, H., Yuan, M., Wu, N. C., Zhu, X., Lee, C.-C. D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.049 · Cited by 347 · see citing works
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Huo, J., Zhao, Y., Ren, J., Zhou, D., Duyvesteyn, H. M. E., Ginn, H. M., Carrique, L., Malinauskas, T., Ruza, R. R., Shah, P. N. M., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.010 · Cited by 317 · see citing works
Self-citationA thermostable, closed SARS-CoV-2 spike protein trimer
Xiong, X., Qu, K., Ciazynska, K. A., Hosmillo, M., Carter, A. P., Ebrahimi, S., Ke, Z., Scheres, S. H. W., Bergamaschi, L., Grice, G. L., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0478-5 · Cited by 313 · see citing works
The Emerging Importance of IgG Fab Glycosylation in Immunity
van de Bovenkamp, F. S., Hafkenscheid, L., Rispens, T., & Rombouts, Y. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502136 · Cited by 307 · see citing works
Caly, L., Druce, J. D., Roberts, J., Bond, K. A., Tran, T., Kostecki, R., Yoga, Y., Naughton, W., Taiaroa, G., Seemann, T., et al. (2020) · The Medical Journal of Australia · doi:10.5694/mja2.50569 · Cited by 305 · see citing works
Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail
Dong, J., Zost, S. J., Greaney, A. J., Starr, T. N., Dingens, A. S., Chen, E. C., Chen, R. E., Case, J. B., Sutton, R. E., Gilchuk, P., et al. (2021) · Nature Microbiology · doi:10.1038/s41564-021-00972-2 · Cited by 285 · see citing works
Self-citationStructural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Zhou, D., Duyvesteyn, H. M. E., Chen, C.-P., Huang, C.-G., Chen, T.-H., Shih, S.-R., Lin, Y.-C., Cheng, C.-Y., Cheng, S.-H., Huang, Y.-C., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0480-y · Cited by 274 · see citing works
Self-citationDu, S., Cao, Y., Zhu, Q.-Y., Yu, P., Qi, F.-F., Wang, G., Du, X., Bao, L., Deng, W., Zhu, H., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.035 · Cited by 249 · see citing works
Self-citationWalter, T. S., Diprose, J. M., Mayo, C., Siebold, C., Pickford, M. G., Carter, L. G., Sutton, G. C., Berrow, N. S., Brown, J., Berry, I. M., et al. (2005) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444905007808 · Cited by 246 · see citing works
Self-citationDisease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19
Chen, X., Pan, Z., Yue, S., Yu, F., Zhang, J., Yang, Y., Li, R., Liu, B., Yang, X., Gao, L., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00301-9 · Cited by 234 · see citing works
Zhang, P., Woen, S., Wang, T., Liau, B., Zhao, S., Chen, C., Yang, Y., Song, Z., Wormald, M. R., Yu, C., et al. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.01.006 · Cited by 212 · see citing works
Furin Cleavage Site Is Key to SARS-CoV-2 PathogenesisPreprint
Johnson, B. A., Xie, X., Kalveram, B., Lokugamage, K. G., Muruato, A. E., Zou, J., Zhang, X., Juelich, T. L., Smith, J. K., Zhang, L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.26.268854 · Cited by 186 · see citing works
Wright, A. M., Tao, M., Kabat, E. A., et al. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07819.x · Cited by 162 · see citing works
Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation
Hurlburt, N. K., Seydoux, E., Wan, Y.-H., Edara, V. V., Stuart, A. B., Feng, J., Suthar, M. S., McGuire, A. T., Stamatatos, L., & Pancera, M. (2020) · Nature Communications · doi:10.1038/s41467-020-19231-9 · Cited by 162 · see citing works
An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
Wu, N. C., Yuan, M., Liu, H., Lee, C.-C. D., Zhu, X., Bangaru, S., Torres, J. L., Caniels, T. G., Brouwer, P. J. M., van Gils, M. J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108274 · Cited by 157 · see citing works
Zhao, G., Du, L., Ma, C., Li, Y., Li, L., Poon, V. K., Wang, L., Yu, F., Zheng, B.-J., Jiang, S., et al. (2013) · Virology Journal · doi:10.1186/1743-422x-10-266 · Cited by 141 · see citing works
DeFrancesco, L. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0732-8 · Cited by 116 · see citing works
Walter, T. S., Diprose, J. M., Brown, J., Pickford, M. G., Owens, R. J., Stuart, D. I., & Harlos, K. (2003) · Journal of Applied Crystallography · doi:10.1107/s0021889803001997 · Cited by 101 · see citing works
Self-citationA plate-based high-throughput assay for virus stability and vaccine formulation
Walter, T. S., Ren, J., Tuthill, T. J., et al. (2012) · Journal of Virological Methods · doi:10.1016/j.jviromet.2012.06.014 · Cited by 98 · see citing works
Self-citationLysosome sorting of β-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor
Zhao, Y., Ren, J., Padilla‐Parra, S., et al. (2014) · Nature Communications · doi:10.1038/ncomms5321 · Cited by 95 · see citing works
Self-citationEnhancing dengue virus maturation using a stable furin over-expressing cell line
Mukherjee, S., Sirohi, D., Dowd, K. A., Chen, Z., Diamond, M. S., Kuhn, R. J., & Pierson, T. C. (2016) · Virology · doi:10.1016/j.virol.2016.06.022 · Cited by 82 · see citing works
Self-citationOff-rate screening for selection of high-affinity anti-drug antibodies
Ylera, F., Harth, S., Waldherr, D., et al. (2013) · Analytical Biochemistry · doi:10.1016/j.ab.2013.07.025 · Cited by 64 · see citing works
Transmission of SARS-CoV-2 from humans to animals and potential host adaptationPreprint
Tan, C. C. S., Lam, S. D., Richard, D., Owen, C. J., Berchtold, D., Orengo, C. A., Nair, M. S., Kuchipudi, S. V., Kapur, V., van Dorp, L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.16.384743 · Cited by 60 · see citing works
Antibody-mediated disruption of the SARS-CoV-2 spike glycoprotein
Wrobel, A. G., Benton, D. J., Hussain, S., Harvey, R., Martin, S. R., Roustan, C., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020) · Nature Communications · doi:10.1038/s41467-020-19146-5 · Cited by 55 · see citing works
Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail
Dong, J., Zost, S. J., Greaney, A. J., Starr, T. N., Dingens, A. S., Chen, E. C., Chen, R. E., Case, J. B., Sutton, R. E., Gilchuk, P., et al. (2021) · doi:10.1101/2021.01.27.428529 · Cited by 55 · see citing works
Self-citationNettleship, J. E., Ren, J., Rahman, N., Berrow, N. S., Hatherley, D., Barclay, A. N., & Owens, R. J. (2008) · Protein Expression and Purification · doi:10.1016/j.pep.2008.06.017 · Cited by 48 · see citing works
Self-citationDynamic Asymmetry Exposes 2019-nCoV Prefusion Spike
Roy, S., Jaiswar, A., & Sarkar, R. (2020) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.0c01431 · Cited by 47 · see citing works
Molecular basis for a germline-biased neutralizing antibody response to SARS-CoV-2Preprint
Clark, S. A., Clark, L. E., Pan, J., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.13.381533 · Cited by 27 · see citing works
Ginn, H. M. (2020) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798320012619 · Cited by 25 · see citing works
Self-citationPlasmablast-derived antibody response to acute SARS-CoV-2 infection in humansPreprint
Huang, K.-Y. A., Tan, T., Chen, T.-H., et al. (2020) · bioRxiv · doi:10.1101/2020.08.28.267526 · Cited by 23 · see citing works
Self-citationCarrique, L., Duyvesteyn, H. M. E., Malinauskas, T., Zhao, Y., Ren, J., Zhou, D., Walter, T. S., Radecke, J., Huo, J., Ruza, R. R., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.13.249177 · Cited by 18 · see citing works
Self-citationCarrique, L., Duyvesteyn, H. M. E., Malinauskas, T., et al. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3656643 · Cited by 10 · see citing works
Self-citationFragility can be a good thing in cancer
Demeyer, A., & Beyaert, R. (2019) · Nature Immunology · doi:10.1038/s41590-019-0564-1 · Cited by 1 · see citing works
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Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
Cao, Y., Wang, J., Jian, F., Xiao, T., Song, W., Yisimayi, A., Huang, W., Li, Q., Wang, P., An, R., et al. (2022) · Nature · doi:10.1038/s41586-021-04385-3 · Cited by 2,006 · see citing works
Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera
Zhou, D., Dejnirattisai, W., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.037 · Cited by 992 · see citing works
Self-citationChen, R. E., Zhang, X., Case, J. B., Winkler, E. S., Liu, Y., VanBlargan, L. A., Liu, J., Errico, J. M., Xie, X., Suryadevara, N., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01294-w · Cited by 881 · see citing works
Self-citationThe biological and clinical significance of emerging SARS-CoV-2 variants
Tao, K., Tzou, P. L., Nouhin, J., Gupta, R. K., de Oliveira, T., Kosakovsky Pond, S. L., Fera, D., & Shafer, R. W. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00408-x · Cited by 1,009 · see citing works
SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
Dejnirattisai, W., Huo, J., Zhou, D., Zahradník, J., Supasa, P., Liu, C., Duyvesteyn, H. M. E., Ginn, H. M., Mentzer, A. J., Tuekprakhon, A., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.046 · Cited by 930 · see citing works
Self-citationReduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum
Liu, C., Ginn, H. M., Dejnirattisai, W., Supasa, P., Wang, B., Tuekprakhon, A., Nutalai, R., Zhou, D., Mentzer, A. J., Zhao, Y., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.020 · Cited by 669 · see citing works
Self-citationAntibody evasion by the P.1 strain of SARS-CoV-2
Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.055 · Cited by 583 · see citing works
Self-citationReduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera
Supasa, P., Zhou, D., Dejnirattisai, W., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Nutalai, R., Tuekprakhon, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.033 · Cited by 460 · see citing works
Self-citationMapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
Greaney, A. J., Starr, T. N., Barnes, C. O., Weisblum, Y., Schmidt, F., Caskey, M., Gaebler, C., Cho, A., Agudelo, M., Finkin, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24435-8 · Cited by 433 · see citing works
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
Yuan, M., Huang, D., Lee, C.-C. D., Wu, N. C., Jackson, A. M., Zhu, X., Liu, H., Peng, L., van Gils, M. J., Sanders, R. W., et al. (2021) · doi:10.1101/2021.02.16.430500 · Cited by 364 · see citing works
Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail
Dong, J., Zost, S. J., Greaney, A. J., Starr, T. N., Dingens, A. S., Chen, E. C., Chen, R. E., Case, J. B., Sutton, R. E., Gilchuk, P., et al. (2021) · Nature Microbiology · doi:10.1038/s41564-021-00972-2 · Cited by 285 · see citing works
Self-citationGreaney, A. J., Loes, A. N., Gentles, L. E., Crawford, K. H. D., Starr, T. N., Malone, K. D., Chu, H. Y., & Bloom, J. D. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abi9915 · Cited by 244 · see citing works
Walls, A. C., Miranda, M. C., Schäfer, A., Pham, M. N., Greaney, A., Arunachalam, P. S., Navarro, M.-J., Tortorici, M. A., Rogers, K., O’Connor, M. A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.015 · Cited by 185 · see citing works
A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants
Schmitz, A. J., Turner, J. S., Liu, Z., Aziati, I. D., Chen, R. E., Joshi, A., Bricker, T. L., Darling, T. L., Adelsberg, D. C., Alsoussi, W. B., et al. (2021) · doi:10.1101/2021.03.24.436864 · Cited by 72 · see citing works
Self-citation
- Authors
- Dejnirattisai, W., Zhou, D., Ginn, H. M., Duyvesteyn, H. M. E., Supasa, P., Case, J. B., Zhao, Y., Walter, T. S., Mentzer, A. J., Liu, C., Wang, B., Paesen, G. C., Slon-Campos, J., López-Camacho, C., Kafai, N. M., Bailey, A. L., Chen, R. E., Ying, B., Thompson, C., Bolton, J., Fyfe, A., Gupta, S., Tan, T. K., Gilbert-Jaramillo, J., James, W., Knight, M., Carroll, M. W., Skelly, D., Dold, C., Peng, Y., Levin, R., Dong, T., Pollard, A. J., Knight, J. C., Klenerman, P., Temperton, N., Hall, D. R., Williams, M. A., Paterson, N. G., Bertram, F. K. R., Siebert, C. A., Clare, D. K., Howe, A., Radecke, J., Song, Y., Townsend, A. R., Huang, K.-Y. A., Fry, E. E., Mongkolsapaya, J., Diamond, M. S., Ren, J., Stuart, D. I., & Screaton, G. R.
- Affiliations
- Centre for Human Genetics (GB)
- Diamond Light Source (GB)
- Washington University in St. Louis (US)
- University of Oxford (GB)
- Worthing Hospital (GB)
- Medway School of Pharmacy (GB)
- Chang Gung University (TW)
- Siriraj Hospital (TH)
- Corresponding author
- Mongkolsapaya, Juthathip
- Diamond, Michael S.
- Ren, Jingshan
- Stuart, David I.
- Screaton, Gavin R.
- ORCID
- Dejnirattisai, Wanwisa
- Zhou, Daming
- Ginn, Helen M.
- Duyvesteyn, Helen M.E.
- Supasa, Piyada
- Case, James Brett
- Zhao, Yuguang
- Walter, Thomas S.
- Mentzer, Alexander J.
- Liu, Chang
- Wang, Beibei
- Paesen, Guido C.
- Slon-Campos, Jose
- López-Camacho, César
- Kafai, Natasha M.
- Bailey, Adam L.
- Chen, Rita E.
- Ying, Baoling
- Thompson, Craig
- Bolton, Jai
- Gupta, Sunetra
- Tan, Tiong Kit
- Gilbert-Jaramillo, Javier
- James, William
- Knight, Michael
- Carroll, Miles W.
- Skelly, Donal
- Dold, Christina
- Peng, Yanchun
- Dong, Tao
- Pollard, Andrew J.
- Knight, Julian C.
- Klenerman, Paul
- Temperton, Nigel
- Hall, David R.
- Williams, Mark A.
- Paterson, Neil G.
- Bertram, Felicity K.R.
- Siebert, C. Alistair
- Clare, Daniel K.
- Howe, Andrew
- Radecke, Julika
- Song, Yun
- Townsend, Alain R.
- Huang, Kuan-Ying A.
- Fry, Elizabeth E.
- Mongkolsapaya, Juthathip
- Diamond, Michael S.
- Ren, Jingshan
- Stuart, David I.
- Screaton, Gavin R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 184
- Issue
- 8
- Pages
- 2183-2200.e22
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7891125
- OpenAlex
- W3129414840
- Cited by
- 371
- References
- 75
- Citations by year
- 2026: 22 · 2025: 34 · 2024: 41 · 2023: 67 · 2022: 115 · 2021: 92
- FWCI
- 25.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (acceptedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- U.S. Environmental Protection Agency
- Cancer Research UK (C375/A17721)
- Medical Research Council (MC_PC_20016, MR/N00065X/1, MC_PC_19060, 204969/Z/16/Z)
- China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica (2018-I2M-2-002)
- Defense Advanced Research Projects Agency (GB-CHC-210183, HR001117S0019)
- NIHR Oxford Biomedical Research Centre
- Department of Health and Social Care
- National Institute for Health Research (109965MA)
- NIH
- Wellcome Trust (060208/Z/00/Z, 203141/Z/16/Z, 095541/A/11/Z, 101122/Z/13/Z, 090532/Z/09/Z)
- Chinese Academy of Medical Sciences
- Helen Hay Whitney Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- SARS-CoV-2, spike protein, receptor binding domain, monoclonal antibodies, neutralizing antibodies, antibody binding sites, epitope mapping, competitive binding assay, antibody structure, N-terminal domain, V gene usage, germline antibodies, therapeutic antibodies
- MeSH terms
- COVID-19, SARS-CoV-2, Animals, Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Binding Sites, Antibody, Chlorocebus aethiops, Cricetulus, Female, Humans, Male, Mice, Transgenic, Models, Molecular, Protein Binding, Vero Cells, CHO Cells, Protein Structure, Tertiary, Mice, Antibodies, Neutralizing, HEK293 Cells, Spike Glycoprotein, Coronavirus
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