Structural basis of receptor recognition by SARS-CoV-2
Open accessPublished version of a preprint
Abstract
A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19 1,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans 3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ACE2 had been identified as the receptor for SARS-CoV and SARS-CoV-2.
“Importantly, ACE2 (angiotensin-converting enzyme 2) had been identified as the receptor for SARS-CoV 4,5 and SARS-CoV-2.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [8]
The ACE2 interaction surface is a small 25-amino-acid patch at the apex of spike, presented to ACE2 when the RBD swings upward.
“The ACE2 interaction surface is a small 25-amino-acid patch at the apex of spike, presented to ACE2 when the RBD swings upward”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Shang et al., 2020
The RBD interacts with ACE2, which is expressed on diverse cell types including cells in the upper and lower respiratory tracts, allowing SARS-CoV-2 to cause respiratory infection.
“The RBD interacts with the cellular receptor angiotensin converting enzyme 2 (ACE2), which is expressed on diverse cell types, including cells in the upper and lower respiratory tracts, allowing SARS-CoV-2 to cause respiratory infection.”
From Antibody evasion by the P.1 strain of SARS-CoV-2 (2021) · cites this paper as Shang et al., 2020
The S2 subunit comprises FP, HR, CH, CD, TMD, CT, and is responsible for mediating fusion between virus and host cell membrane.
“The S2 subunit comprises the fusion peptide (FP), double heptad repeat (HR), central helix region (CH), connector domain (CD), transmembrane domain (TMD), and cytoplasmic tail (CT), and the S2 subunit is responsible for mediating the fusion between the virus and the host cell membrane233–236”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [234]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884 · see citing works
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · 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
Clinical characteristics of coronavirus disease 2019 in China
Guan, W.-J., Ni, Z.-Y., Hu, Y., Liang, W.-H., Ou, C.-Q., He, J.-X., Liu, L., Shan, H., Lei, C.-L., Hui, D. S. C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002032 · Cited by 30,246 · see citing works
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969 · 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
Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia
Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K. S. M., Lau, E. H. Y., Wong, J. Y., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001316 · Cited by 16,575 · see citing works
Overview of the <i>CCP</i> 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · 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
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923 · see citing works
Origin and evolution of pathogenic coronaviruses
Cui, J., Li, F., & Shi, Z. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0118-9 · Cited by 5,539 · see citing works
Self-citationWan, Y., Shang, J., Graham, R., Baric, R. S., & Li, F. (2020) · Journal of Virology · doi:10.1128/jvi.00127-20 · Cited by 4,341 · see citing works
Self-citationLetko, M., Marzi, A., & Munster, V. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0688-y · Cited by 3,109 · see citing works
Coronavirus as a possible cause of severe acute respiratory syndrome
Peiris, M. J. S., Lai, S., Poon, L. L. M., Guan, Y., Yam, L., Lim, W., Nicholls, J. M., Yee, W., Yan, W., Cheung, M., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13077-2 · Cited by 2,916 · see citing works
Structure, Function, and Evolution of Coronavirus Spike Proteins
Li, F. (2016) · Annual Review of Virology · doi:10.1146/annurev-virology-110615-042301 · Cited by 2,740 · see citing works
Self-citationA Major Outbreak of Severe Acute Respiratory Syndrome in Hong Kong
Lee, N. L. S., Hui, D. S. C., Wu, A. K. L., Chan, P. K. S., Cameron, P. A., Joynt, G. M., Ahuja, A. T., Yung, M. Y., Leung, C. B., To, K. F., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030685 · Cited by 2,631 · see citing works
Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor
Li, F., Li, W., Farzan, M., & Harrison, S. C. (2005) · Science · doi:10.1126/science.1116480 · Cited by 2,031 · see citing works
Self-citationCoronaviruses post-SARS: update on replication and pathogenesis
Perlman, S. M., & Netland, J. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2147 · Cited by 1,766 · see citing works
The spike protein of SARS-CoV — a target for vaccine and therapeutic development
Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B.-J., & Jiang, S. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2090 · Cited by 1,649 · see citing works
Receptor and viral determinants of SARS‐coronavirus adaptation to human ACE2
Li, W., Zhang, C., Sui, J., Kuhn, J. H., Moore, M. J., Luo, S., Wong, S.-K., Huang, I., Xu, K., Vasilieva, N. Y., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600640 · Cited by 976 · see citing works
Sui, J., Li, W., Murakami, A., Tamin, A., Matthews, L. J., Wong, S. K., Moore, M. J., Tallarico, A. S. C., Olurinde, M., Choe, H., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307140101 · Cited by 540 · see citing works
MERS-CoV spike protein: a key target for antivirals
Du, L., Yang, Y., Zhou, Y., Lu, L., Li, F., & Jiang, S. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1271415 · Cited by 301 · see citing works
Yang, Y., Du, L., Liu, C., Wang, L., Ma, C., Tang, J., Baric, R. S., Jiang, S., & Li, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405889111 · Cited by 281 · see citing works
Self-citationMechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus
Wu, K., Peng, G., Wilken, M. S., Geraghty, R. J., & Li, F. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.325803 · Cited by 246 · see citing works
Self-citationIsolation and Characterization of 2019-nCoV-like Coronavirus from Malayan PangolinsPreprint
Xiao, K., Zhai, J., Feng, Y., Zhou, N., Zhang, X., Zou, J., Li, N., Guo, Y., Li, X., Shen, X., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.17.951335 · Cited by 200 · see citing works
Li, F. (2008) · Journal of Virology · doi:10.1128/jvi.00442-08 · Cited by 183 · see citing works
Self-citationDu, L., Tai, W., Yang, Y., Zhao, G., Zhu, Q., Sun, S., Liu, C., Tao, X., Tseng, C.-T. K., Perlman, S. M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13473 · Cited by 120 · see citing works
Self-citationSun, C., Chen, L., Yang, J., Luo, C., Zhang, Y., Li, J., Yang, J., Zhang, J., & Xie, L. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.16.951723 · Cited by 77 · see citing works
Self-citationArtifacts and limitations of enzyme immunoassay
Pesce, A. J., & Michael, J. G. (1992) · Journal of Immunological Methods · doi:10.1016/0022-1759(92)90070-a · Cited by 72 · see citing works
Salt Bridge in Aqueous Solution: Strong Structural Motifs but Weak Enthalpic Effect
Pylaeva, S. A., Brehm, M., & Sebastiani, D. (2018) · Scientific Reports · doi:10.1038/s41598-018-31935-z · Cited by 69 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [17]Lan J Crystal structure of the 2019-nCoV spike receptor-binding domain bound with the ACE2 receptor. bioRxiv, 2020.2002.2019.956235, doi: 10.1101/2020.02.19.956235 (2020). · DOI
Cited by
Sorted by citations
Nalbandian, A., Sehgal, K., Gupta, A., Madhavan, M. V., McGroder, C., Stevens, J. S., Cook, J. R., Nordvig, A. S., Shalev, D., Sehrawat, T. S., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01283-z · Cited by 4,862 · see citing works
The trinity of COVID-19: immunity, inflammation and intervention
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. P. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0311-8 · Cited by 4,360 · see citing works
Extrapulmonary manifestations of COVID-19
Gupta, A., Madhavan, M. V., Sehgal, K., Nair, N., Mahajan, S., Sehrawat, T. S., Bikdeli, B., Ahluwalia, N., Ausiello, J. C., Wan, E. Y., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0968-3 · Cited by 3,185 · see citing works
Cell entry mechanisms of SARS-CoV-2
Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., & Li, F. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003138117 · Cited by 3,142 · see citing works
Self-citationStarr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.012 · Cited by 1,956 · see citing works
Human organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187 · 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
Gheblawi, M., Wang, K., Viveiros, A., Nguyen, Q., Zhong, J.-C., Turner, A. J., Raizada, M. K., Grant, M. B., & Oudit, G. Y. (2020) · Circulation Research · doi:10.1161/circresaha.120.317015 · Cited by 1,882 · see citing works
Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization
Zuo, T., Zhang, F., Lui, G. C. Y., Yeoh, Y. K., Li, A. Y. L., Zhan, H., Wan, Y., Chung, A. C. K., Cheung, C. P., Chen, N., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.05.048 · Cited by 1,537 · see citing works
Self-citationSARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
Barnes, C. O., Jette, C. A., Abernathy, M. E., Dam, K.-M. A., Esswein, S. R., Gristick, H. B., Malyutin, A. G., Sharaf, N. G., Huey-Tubman, K. E., Lee, Y. E., et al. (2020) · Nature · doi:10.1038/s41586-020-2852-1 · Cited by 1,599 · see citing works
A 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
SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract
Hou, Y. J., Okuda, K., Edwards, C. E., Martinez, D. R., Asakura, T., Dinnon, K. H., Kato, T., Lee, R. E., Yount, B. L., Mascenik, T. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.042 · Cited by 1,488 · see citing works
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
Brouwer, P. J. M., Caniels, T. G., van der Straten, K., Snitselaar, J. L., Aldon, Y., Bangaru, S., Torres, J. L., Okba, N. M. A., Claireaux, M., Kerster, G., et al. (2020) · Science · doi:10.1126/science.abc5902 · Cited by 1,140 · see citing works
Markov, P. V., Ghafari, M., Beer, M., Lythgoe, K., Simmonds, P., Stilianakis, N. I., & Katzourakis, A. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00878-2 · Cited by 1,179 · 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
Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
Yin, W., Mao, C., Luan, X., Shen, D.-D., Shen, Q., Su, H., Wang, X., Zhou, F., Zhao, W., Gao, M., et al. (2020) · Science · doi:10.1126/science.abc1560 · Cited by 1,219 · see citing works
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., et al. (2020) · doi:10.1101/2020.12.21.20248640 · Cited by 2,535 · see citing works
Greaney, A. J., Starr, T. N., Gilchuk, P., Zost, S. J., Binshtein, E., Loes, A. N., Hilton, S. K., Huddleston, J., Eguia, R., Crawford, K. H. D., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.11.007 · Cited by 1,016 · 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
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant
Yurkovetskiy, L., Wang, X., Pascal, K. E., Tomkins-Tinch, C., Nyalile, T. P., Wang, Y., Baum, A., Diehl, W. E., Dauphin, A., Carbone, C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.032 · Cited by 1,025 · see citing works
SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity
Zhang, L., Jackson, C. B., Mou, H., Ojha, A., Peng, H., Quinlan, B. D., Rangarajan, E. S., Pan, A., Vanderheiden, A., Suthar, M. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19808-4 · Cited by 1,387 · see citing works
The protein expression profile of ACE2 in human tissues
Hikmet, F., Méar, L., Edvinsson, Å., Micke, P., Uhlén, M., & Lindskog, C. (2020) · Molecular Systems Biology · doi:10.15252/msb.20209610 · Cited by 1,016 · see citing works
Molecular Architecture of the SARS-CoV-2 Virus
Yao, H., Song, Y., Chen, Y., Wu, N., Xu, J., Sun, C., Zhang, J., Weng, T., Zhang, Z., Wu, Z., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.018 · Cited by 1,060 · see citing works
“The S protein binds to the cellular surface receptor angiotensin-converting enzyme 2 (ACE2) through the receptor binding domain (RBD), an essential step for membrane fusion (Hoffmann et al., 2020; Lan et al., 2020; Shang et al., 2020; Wang et al., 2020; Yan et al., 2020; Zhou et al., 2020).”
The 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
Barnes, 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
SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development
Wang, M.-Y., Zhao, R., Gao, L.-J., Gao, X.-F., Wang, D.-P., & Cao, J.-M. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.587269 · Cited by 874 · see citing works
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
Starr, T. N., Greaney, A. J., Addetia, A., Hannon, W. W., Choudhary, M. C., Dingens, A. S., Li, J. Z., & Bloom, J. D. (2021) · Science · doi:10.1126/science.abf9302 · Cited by 743 · see citing works
Liu, Z., VanBlargan, L. A., Bloyet, L.-M., Rothlauf, P. W., Chen, R. E., Stumpf, S., Zhao, H., Errico, J. M., Theel, E. S., Liebeskind, M. J., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.01.014 · Cited by 725 · see citing works
“Residue F486 is located on the top of the hACE2 contact loop of RBD, and the presence of a large hydrophobic residue facilitates efficient receptor engagement (Lan et al., 2020; Shang et al., 2020).”
BackgroundLoss 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
De novo design of picomolar SARS-CoV-2 miniprotein inhibitors
Cao, L., Goreshnik, I., Coventry, B., Case, J. B., Miller, L., Kozodoy, L., Chen, R. E., Carter, L., Walls, A. C., Park, Y.-J., et al. (2020) · Science · doi:10.1126/science.abd9909 · Cited by 742 · see citing works
Immune response, inflammation, and the clinical spectrum of COVID-19
García, L. F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01441 · Cited by 739 · see citing works
Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa
Tegally, H., Moir, M., Everatt, J., Giovanetti, M., Scheepers, C., Wilkinson, E., Subramoney, K., Makatini, Z., Moyo, S., Amoako, D. G., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01911-2 · Cited by 707 · see citing works
A thermostable mRNA vaccine against COVID-19
Zhang, N.-N., Li, X.-F., Deng, Y.-Q., Zhao, H., Huang, Y.-J., Yang, G., Huang, W.-J., Gao, P., Zhou, C., Zhang, R.-R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.024 · Cited by 671 · see citing works
“The structures of the SARS-CoV-2 RBD alone and the RBD-ACE2 and RBD-monoclonal antibody complexes were resolved in record time at high resolution (Lan et al., 2020; Shang et al., 2020; Walls et al., 2020), which further improves our understanding of this vaccine target.”
Antibody 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
Thomson, E. C., Rosen, L. E., Shepherd, J. G., Spreafico, R., da Silva Filipe, A., Wojcechowskyj, J. A., Davis, C., Piccoli, L., Pascall, D. J., Dillen, J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.037 · Cited by 606 · see citing works
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
Tortorici, M. A., Beltramello, M., Lempp, F. A., Pinto, D., Dang, H. V., Rosen, L. E., McCallum, M., Bowen, J., Minola, A., Jaconi, S., et al. (2020) · Science · doi:10.1126/science.abe3354 · Cited by 510 · see citing works
Walls, A. C., Fiala, B., Schäfer, A., Wrenn, S., Pham, M. N., Murphy, M., Tse, L. V., Shehata, L., O’Connor, M. A., Chen, C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.043 · Cited by 532 · see citing works
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0468-7 · Cited by 544 · see citing works
Starr, T. N., Greaney, A. J., Dingens, A. S., & Bloom, J. D. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100255 · Cited by 470 · see citing works
Scaffolding protein functional sites using deep learning
Wang, J., Lisanza, S., Juergens, D., Tischer, D., Watson, J. L., Castro, K. M., Ragotte, R., Saragovi, A., Milles, L. F., Baek, M., et al. (2022) · Science · doi:10.1126/science.abn2100 · Cited by 487 · see citing works
Lifting the mask on neurological manifestations of COVID-19
Pezzini, A., & Padovani, A. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0398-3 · Cited by 447 · see citing works
Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection
Butowt, R., & von Bartheld, C. S. (2021) · The Neuroscientist · doi:10.1177/1073858420956905 · Cited by 345 · see citing works
On the origin and evolution of SARS-CoV-2
Singh, D., & Yi, S. V. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00604-z · Cited by 281 · see citing works
Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2
Youk, J., Kim, T., Evans, K. V., Jeong, Y.-I., Hur, Y., Hong, S. P., Kim, J. H., Yi, K., Kim, S. Y., Na, K. J., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.10.004 · Cited by 266 · see citing works
Engineered ACE2 receptor traps potently neutralize SARS-CoV-2
Glasgow, A., Glasgow, J., Limonta, D., Solomon, P., Lui, I., Zhang, Y., Nix, M. A., Rettko, N. J., Zha, S., Yamin, R., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016093117 · Cited by 251 · see citing works
Cherian, S., Potdar, V., Jadhav, S., Yadav, P., Gupta, N., Das, M., Rakshit, P., Singh, S., Abraham, P., Panda, S., et al. (2021) · doi:10.1101/2021.04.22.440932 · Cited by 730 · see citing works
“Wiley Online Library; 2017; 1(1):33–46.”
BackgroundA Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection
Alsoussi, W. B., Turner, J. S., Case, J. B., Zhao, H., Schmitz, A. J., Zhou, J. Q., Chen, R. E., Lei, T., Rizk, A. A., McIntire, K. M., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000583 · Cited by 181 · see citing works
De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
Linsky, T. W., Vergara, R., Codina, N., Nelson, J. W., Walker, M. J., Su, W., Barnes, C. O., Hsiang, T.-Y., Esser-Nobis, K., Yu, K., et al. (2020) · Science · doi:10.1126/science.abe0075 · Cited by 216 · 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
“SARS-CoV-2 infects host cells through the attachment of the viral transmembrane spike (S) glycoprotein to angiotensin-converting enzyme 2 (ACE2), followed by fusion of the viral and host membranes (Hoffmann et al., 2020; Lan et al., 2020; Letko et al., 2020; Shang et al., 2020; Walls et al., 2020a; Wang et al., 2020;…”
Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape
Ku, Z., Xie, X., Davidson, E., Ye, X., Su, H., Menachery, V. D., Li, Y., Yuan, Z., Zhang, X., Muruato, A. E., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20789-7 · Cited by 160 · see citing works
COVID-19, Myocarditis and Pericarditis
Fairweather, D., Beetler, D. J., Di Florio, D. N., Musigk, N., Heidecker, B., & Cooper, L. T. (2023) · Circulation Research · doi:10.1161/circresaha.123.321878 · Cited by 181 · see citing works
Kutter, J. S., de Meulder, D., Bestebroer, T. M., Lexmond, P., Mulders, A., Richard, M., Fouchier, R. A. M., & Herfst, S. (2021) · Nature Communications · doi:10.1038/s41467-021-21918-6 · Cited by 176 · see citing works
Shan, S., Luo, S., Yang, Z., Hong, J., Su, Y., Ding, F., Fu, L., Li, C., Chen, P., Ma, J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2122954119 · Cited by 157 · see citing works
An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants
Chan, K. K., Tan, T. J. C., Narayanan, K. K., & Procko, E. (2021) · Science Advances · doi:10.1126/sciadv.abf1738 · Cited by 152 · see citing works
A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2
Tai, W., Zhang, X., Drelich, A., Shi, J., Hsu, J. C., Luchsinger, L., Hillyer, C. D., Tseng, C.-T. K., Jiang, S., & Du, L. (2020) · Cell Research · doi:10.1038/s41422-020-0387-5 · Cited by 151 · see citing works
Tsutsui, M., Gerayeli, F., & Sin, D. D. (2021) · International Journal of Chronic Obstructive Pulmonary Disease · doi:10.2147/copd.s263031 · Cited by 147 · see citing works
Klimstra, W. B., Tilston-Lunel, N. L., Nambulli, S., Boslett, J., McMillen, C. M., Gilliland, T., Dunn, M. D., Sun, C., Wheeler, S. E., Wells, A., et al. (2020) · Journal of General Virology · doi:10.1099/jgv.0.001481 · Cited by 137 · see citing works
Ashary, N., Bhide, A., Chakraborty, P., Colaco, S., Mishra, A., Chhabria, K., Jolly, M. K., & Modi, D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00783 · Cited by 121 · see citing works
Alquisiras-Burgos, I., Peralta-Arrieta, I., Alonso-Palomares, L. A., Zacapala-Gómez, A. E., Salmerón-Bárcenas, E. G., & Aguilera, P. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02134-7 · Cited by 115 · see citing works
COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
Rysz, S., Al-Saadi, J., Sjöström, A., Farm, M., Campoccia Jalde, F., Plattén, M., Eriksson, H., Klein, M., Vargas-Paris, R., Nyrén, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22713-z · Cited by 111 · see citing works
Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier?
Burks, S. M., Rosas-Hernandez, H., Alejandro Ramirez-Lee, M., Cuevas, E., & Talpos, J. C. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.12.031 · Cited by 97 · see citing works
Liu, Z., VanBlargan, L. A., Bloyet, L.-M., Rothlauf, P. W., Chen, R. E., Stumpf, S., Zhao, H., Errico, J. M., Theel, E. S., Liebeskind, M. J., et al. (2020) · doi:10.1101/2020.11.06.372037 · Cited by 135 · see citing works
Martínez-Mármol, R., Giordano-Santini, R., Kaulich, E., Cho, A.-N., Przybyla, M., Riyadh, M. A., Robinson, E., Chew, K. Y., Amor, R., Meunier, F. A., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg2248 · Cited by 94 · see citing works
Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models
Kalnin, K. V., Plitnik, T., Kishko, M., Zhang, J., Zhang, D., Beauvais, A., Anosova, N. G., Tibbitts, T., DiNapoli, J., Ulinski, G., et al. (2021) · npj Vaccines · doi:10.1038/s41541-021-00324-5 · Cited by 82 · see citing works
Presence of antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 in COVID-19 plasma
Tso, F. Y., Lidenge, S. J., Poppe, L. K., Peña, P. B., Privatt, S. R., Bennett, S. J., Ngowi, J. R., Mwaiselage, J., Belshan, M., Siedlik, J. A., et al. (2021) · PLOS ONE · doi:10.1371/journal.pone.0247640 · Cited by 68 · see citing works
Pentón-Rol, G., Marín-Prida, J., & McCarty, M. F. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210408123807 · Cited by 73 · see citing works
Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
Guo, H., Hu, B., Si, H.-R., Zhu, Y., Zhang, W., Li, B., Li, A., Geng, R., Lin, H.-F., Yang, X.-L., et al. (2021) · Emerging Microbes & Infections · doi:10.1080/22221751.2021.1956373 · Cited by 71 · see citing works
Zang, J., Gu, C., Zhou, B., Zhang, C., Yang, Y., Xu, S., Bai, L., Zhang, R., Deng, Q., Yuan, Z., et al. (2020) · Cell Discovery · doi:10.1038/s41421-020-00199-1 · Cited by 67 · see citing works
Mesenchymal stem cell immunomodulation: in pursuit of controlling COVID-19 related cytokine storm
Song, N., Wakimoto, H., Rossignoli, F., Bhere, D., Ciccocioppo, R., Chen, K.-S., Khalsa, J. K., Mastrolia, I., Samarelli, A. V., Dominici, M., et al. (2021) · Stem Cells · doi:10.1002/stem.3354 · Cited by 62 · see citing works
Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients
Duan, Y.-Q., Xia, M.-H., Ren, L., Zhang, Y.-F., Ao, Q.-L., Xu, S.-P., Kuang, D., Liu, Q., Yan, B., Zhou, Y.-W., et al. (2020) · Current Medical Science · doi:10.1007/s11596-020-2225-x · Cited by 59 · see citing works
Verma, A. K., & Aggarwal, R. (2021) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13812 · Cited by 54 · see citing works
Kumar, S., Karuppanan, K., & Subramaniam, G. (2022) · doi:10.1101/2022.02.11.480029 · Cited by 223 · see citing works
Steffen, T. L., Stone, E. T., Hassert, M., Geerling, E., Grimberg, B. T., Espino, A. M., Pantoja, P., Climent, C., Hoft, D. F., George, S. L., et al. (2020) · doi:10.1101/2020.08.21.261727 · Cited by 25 · see citing works
Coronaviruses closely related to the pandemic virus discovered in Japan and Cambodia
Mallapaty, S. (2020) · Nature · doi:10.1038/d41586-020-03217-0 · Cited by 31 · see citing works
Kim, J., Mukherjee, A., Nelson, D., Jozic, A., & Sahay, G. (2020) · doi:10.1101/2020.07.24.205583 · Cited by 28 · see citing works
Devaux, C. A., & Camoin-Jau, L. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1042200 · Cited by 20 · see citing works
Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
Kalnin, K. V., Plitnik, T., Kishko, M., Zhang, J., Zhang, D., Beauvais, A., Anosova, N. G., Tibbitts, T., DiNapoli, J. M., Huang, P.-W. D., et al. (2020) · doi:10.1101/2020.10.14.337535 · Cited by 18 · 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
- Authors
- Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Li, Fang
- Venue
- Nature
- Published
- 2020-03-30
- Volume
- 581
- Issue
- 7807
- Pages
- 221-224
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7328981
- OpenAlex
- W3013800395
- Cited by
- 3,661
- References
- 32
- Citations by year
- 2026: 90 · 2025: 172 · 2024: 261 · 2023: 386 · 2022: 699 · 2021: 1140 · 2020: 910 · 2019: 1 · 2012: 1
- FWCI
- 102.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐ AC02‐06CH11357, AC02‐06CH11357, S10OD021527, contract DE-AC02-06CH11357, 06CH11357, DE-AC02-)
- National Institutes of Health (1s10od021527-01, DE-AC02–06CH11357)
- National Institute of General Medical Sciences (R35GM118047, P30GM124165)
- National Institute of Allergy and Infectious Diseases (R01AI110700, R01AI089728)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- SARS-CoV-2, spike protein receptor-binding domain, ACE2, receptor recognition, host-virus interaction, RaTG13, SARS-CoV, binding affinity, animal-to-human transmission, COVID-19 pandemic, crystal structure
- MeSH terms
- Protein Domains, Eutheria, Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Binding Sites, China, Chiroptera, Crystallization, Disease Reservoirs, Humans, Peptidyl-Dipeptidase A, Models, Molecular, Pneumonia, Viral, Protein Binding, Receptors, Virus, Zoonoses, Coronavirus, Coronavirus Infections, Crystallography, X-Ray, Severe acute respiratory syndrome-related coronavirus, Protein Stability, Pandemics, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
