CoChat
Sign Up
PreprintCited by 19Animal Virus Infections StudiesSARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approaches

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Neutralizing Antibodies Reveal Cryptic Vulnerabilities and Interdomain Crosstalk in the Porcine Deltacoronavirus Spike

Open access
Bosch, Berend-Jan, Du, Wenjuan, Debski-Antoniak, Oliver, Drabek, Dubravka, Haperen, Rien van, Dortmondt, Melissa van, Lee, Joline van der, Drulyte, Ieva, Kuppeveld, Frank van, Grosveld, Frank, Hurdiss, Daniel·2024·Nature Communications
DOI 10.21203/rs.3.rs-3726585/v1PMC PMC11193727

Preprint — published as 10.1038/s41467-024-49693-0 · Paper page

Open this paper in CoChat — free account

Abstract

Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen in pigs that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here we generated and characterized a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to the APN receptor. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide critical structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.

Overview

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.21203/rs.3.rs-3726585/v1

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

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.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 88

  1. Su S et al (2016) Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol 24:490–502 · DOI
  2. Cui J, Li F, Shi Z (2019) Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 17:181–192 · DOI
  3. Zhong NS et al (2003) Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet 362:1353–1358 · DOI
  4. Ksiazek TG et al (2003) A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348:1953–1966 · DOI
  5. Drosten C et al (2003) Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348:1967–1976 · DOI · Paper page
  6. Lau SKP et al (2005) Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc. Natl. Acad. Sci. U. S. A. 102, 14040–14045
  7. Yang Xing-Lou et al (2016) Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. J Virol 90:3253–3256 · DOI
  8. Hu B et al (2017) Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 13:e1006698 · DOI
  9. Guan Y et al (2003) Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China. Science 302:276–278 · DOI
  10. Kan B et al (2005) Molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms. J Virol 79:11892–11900 · DOI
  11. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier R (2012) A. M. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367:1814–1820 · DOI
  12. Alagaili AN et al (2014) Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. mBio 5:884
  13. Hemida MG et al (2013) Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill 18:20659 · DOI
  14. Tan W et al (2020) A Novel Coronavirus Genome Identified in a Cluster of Pneumonia Cases — Wuhan, China 2019 – 2020. China CDC Weekly 2:61–62 · DOI
  15. Zhou P et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270–273 · DOI · Paper page
  16. Murakami S et al (2020) Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS-CoV-2, Japan. Emerg Infect Dis 26:3025–3029 · DOI
  17. Wacharapluesadee S et al (2021) Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia. Nat Commun 12:972 · DOI
  18. Zhou H et al (2020) A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein. Curr Biol 30:2196–2203e3 · DOI
  19. Zhou H et al (2021) Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses. Cell 184:4380–4391e14 · DOI
  20. Temmam S et al (2022) Bat coronaviruses related to SARS-CoV-2 and infectious for human cells. Nature 604:330–336 · DOI
  21. Lam TT et al (2020) Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature 583:282–285 · DOI
  22. Niu S et al (2021) Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin. EMBO J 40:e107786 · DOI
  23. Lu R et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 395:565–574 · DOI · Paper page
  24. Woo PCY et al (2012) Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol 86:3995–4008 · DOI
  25. Wang L, Byrum B, Zhang Y (2014) Detection and genetic characterization of deltacoronavirus in pigs, Ohio, USA, 2014. Emerg Infect Dis 20:1227–1230 · DOI
  26. Le VP et al (2018) A novel strain of porcine deltacoronavirus in Vietnam. Arch Virol 163:203–207 · DOI
  27. Lorsirigool A et al (2016) The first detection and full-length genome sequence of porcine deltacoronavirus isolated in Lao PDR. Arch Virol 161:2909–2911 · DOI
  28. Song D et al (2015) Newly Emerged Porcine Deltacoronavirus Associated With Diarrhoea in Swine in China: Identification, Prevalence and Full-Length Genome Sequence Analysis. Transbound Emerg Dis 62:575–580 · DOI
  29. Kim H et al (2023) Genetic Characterization and Evolution of Porcine Deltacoronavirus Isolated in the Republic of Korea in 2022. Pathogens 12, 686. 10.3390/pathogens12050686 · DOI
  30. Hu H et al (2015) Isolation and characterization of porcine deltacoronavirus from pigs with diarrhea in the United States. J Clin Microbiol 53:1537–1548 · DOI
  31. Ma Y et al (2015) Origin, evolution, and virulence of porcine deltacoronaviruses in the United States. mBio 6:64
  32. Jung K et al (2015) Pathogenicity of 2 porcine deltacoronavirus strains in gnotobiotic pigs. Emerg Infect Dis 21:650–654 · DOI
  33. Jung K, Hu H, Saif LJ (2017) Calves are susceptible to infection with the newly emerged porcine deltacoronavirus, but not with the swine enteric alphacoronavirus, porcine epidemic diarrhea virus. Arch Virol 162:2357–2362 · DOI
  34. Liang Q et al (2019) Susceptibility of Chickens to Porcine Deltacoronavirus Infection. Viruses 11:573. 10.3390/v11060573 · DOI
  35. Boley PA et al (2020) Porcine Deltacoronavirus Infection and Transmission in Poultry, United States(1). Emerg Infect Dis 26:255–265 · DOI
  36. Lednicky JA et al (2021) Independent infections of porcine deltacoronavirus among Haitian children. Nature 600:133–137 · DOI
  37. Li F (2015) Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol 89:1954–1964 · DOI
  38. Hulswit RJG, de Haan CAM, Bosch B (2016) -. Chapter Two - Coronavirus Spike Protein and Tropism Changes. Adv Virus Res 96:29–57 · DOI
  39. Yuan Y et al (2017) Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun 8:15092 · DOI
  40. Wrapp D et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:1260–1263 · DOI · Paper page
  41. Yan R et al (2021) Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2. Cell Res 31:717–719 · DOI
  42. Gui M et al (2017) Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res 27:119–129 · DOI
  43. Li W et al (2018) Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility. Proceedings of the National Academy of Sciences 115, E5135-E5143
  44. Wang B et al (2018) Porcine Deltacoronavirus Engages the Transmissible Gastroenteritis Virus Functional Receptor Porcine Aminopeptidase N for Infectious Cellular Entry. J Virol 92:e00318–e00318 Print 2018 Jun 15 · DOI
  45. Wang X et al (2022) Genome-Wide CRISPR/Cas9 Screen Reveals a Role for SLC35A1 in the Adsorption of Porcine Deltacoronavirus. J Virol 96:e0162622–e0162622 Epub 2022 Dec 1 · DOI
  46. Zhang Y, Han L, Xia L, Yuan Y, Hu H (2020) Assessment of hemagglutination activity of porcine deltacoronavirus. J Vet Sci 21:e12 · DOI
  47. Yuan Y et al (2021) Porcine Deltacoronavirus Utilizes Sialic Acid as an Attachment Receptor and Trypsin Can Influence the Binding Activity. Viruses 13:2442. 10.3390/v13122442 · DOI
  48. Corti D, Purcell LA, Snell G, Veesler D (2021) Tackling COVID-19 with neutralizing monoclonal antibodies. Cell 184:3086–3108 · DOI
  49. Chi X et al (2020) A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science 369:650–655 · DOI · Paper page
  50. Barnes CO et al (2020) SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 588:682–687 · DOI · Paper page
  51. Liu L et al (2020) Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584:450–456 · DOI · Paper page
  52. McCallum M et al (2021) N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184:2332–2347e16 · DOI · Paper page
  53. Wang C et al (2022) Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes. Nat Commun 13:2921–2920 · DOI
  54. Xiang J et al (2022) Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein. Commun Biology 5:1179 · DOI
  55. Xiong X et al (2018) Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections. J Virol 92:e01628–e01617 Print 2018 Feb 15 · DOI
  56. Martí D, Torras J, Bertran O, Turon P, Alemán C (2021) Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein. Comput Struct Biotechnol J 19:1848–1862 · DOI
  57. Ji W et al (2022) Structures of a deltacoronavirus spike protein bound to porcine and human receptors. Nat Commun 13:1467 · DOI
  58. Shang J et al (2018) Cryo-Electron Microscopy Structure of Porcine Deltacoronavirus Spike Protein in the Prefusion State. J Virol 92:e01556–e01517 · DOI
  59. Cai C et al (2020) Distinct conformational states of SARS-CoV-2 spike protein. Science 369:1586–1592 · DOI · Paper page
  60. Zhang J et al (2021) Structural impact on SARS-CoV-2 spike protein by D614G substitution. Science 372:525–530 · DOI
  61. Shang J et al (2018) Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins. PLoS Pathog 14:e1007009 · DOI
  62. Tortorici MA et al (2019) Structural basis for human coronavirus attachment to sialic acid receptors. Nature Structural & Molecular Biology 26:481–489 · DOI
  63. Walls AC et al (2016) Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer. Nature 531:114–117 · DOI
  64. Walls AC et al (2016) Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nature Structural & Molecular Biology 23:899–905 · DOI
  65. Yang T et al (2020) Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans. Proceedings of the National Academy of Sciences 117, 1438–1446
  66. Song X et al (2021) Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes. Nat Commun 12:141 · DOI
  67. Pronker MF et al (2023) Sialoglycan binding triggers spike opening in a human coronavirus. Nature · DOI
  68. Huo J et al (2020) Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike. Cell Host & Microbe 28:445–454e6 · DOI
  69. Zhou D et al (2020) Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nature Structural & Molecular Biology 27:950–958 · DOI · Paper page
  70. Piccoli L et al (2020) Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology. Cell 183:1024–1042e21 · DOI · Paper page
  71. Lv Z et al (2020) Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Science 369:1505–1509 · DOI
  72. Du W et al (2022) An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern. Sci Immunol 7:eabp9312 · DOI
  73. Punjani A, Rubinstein JL, Fleet DJ, Brubaker MA (2017) cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat Methods 14:290–296 · DOI · Paper page
  74. Punjani A, Zhang H, Fleet DJ (2020) Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nat Methods 17:1214–1221 · DOI
  75. Pettersen EF et al (2004) UCSF Chimera–a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612 · DOI
  76. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60:2126–2132 · DOI · Paper page
  77. Mirdita M et al (2022) ColabFold: making protein folding accessible to all. Nat Methods 19:679–682 · DOI · Paper page
  78. Emsley P, Crispin M (2018) Structural analysis of glycoproteins: building N-linked glycans with Coot. Acta Crystallogr D Struct Biol 74:256–263 · DOI
  79. Kidmose RT et al (2019) Namdinator - automatic molecular dynamics flexible fitting of structural models into cryo-EM and crystallography experimental maps. IUCrJ 6:526–531 · DOI
  80. Headd JJ et al (2012) Use of knowledge-based restraints in phenix.refine to improve macromolecular refinement at low resolution. Acta Crystallogr D Biol Crystallogr 68:381–390 · DOI
  81. Chen VB et al (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66:12–21 · DOI · Paper page
  82. Barad BA et al (2015) EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. Nat Methods 12:943–946 · DOI · Paper page
  83. Agirre J, Davies G, Wilson K, Cowtan K (2015) Carbohydrate anomalies in the PDB. Nat Chem Biol 11:303 · DOI
  84. Agirre J et al (2015) Privateer: software for the conformational validation of carbohydrate structures. Nat Struct Mol Biol 22:833–834 · DOI
  85. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372:774–797 · DOI
  86. Laskowski RA, Swindells MB (2011) LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786 · DOI
  87. Pettersen EF et al (2021) UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci 30:70–82 · DOI
  88. Morin A et al (2013) Collaboration gets the most out of software. eLife 2:e01456 · DOI

Metadata

Authors
Bosch, B.-J., Du, W., Debski-Antoniak, O., Drabek, D., Haperen, R. V., Dortmondt, M. V., Lee, J. V. D., Drulyte, I., Kuppeveld, F. V., Grosveld, F., & Hurdiss, D.
Affiliations
  • Utrecht University (NL)
  • Erasmus MC (NL)
  • ErasmusMC
  • Utrecht university
  • Thermo Fisher Scientific (Netherlands) (NL)
  • Utrecht University
Corresponding author
  • Bosch, Berend-Jan
  • Hurdiss, Daniel
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-01-09
Volume
15
Issue
1
Pages
5330-5330
ISSN
2041-1723 (ISSN-L)
DOI
10.21203/rs.3.rs-3726585/v1
PMC
PMC11193727
OpenAlex
W4399914567
Cited by
19
References
1
Citations by year
2026: 11 · 2025: 7 · 2024: 1
FWCI
5.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • Bill and Melinda Gates Foundation
  • University of Dundee
  • European Federation of Pharmaceutical Industries and Associations
  • European Commission (101005077, HORIZON2020)
  • Innovative Medicines Initiative (101005077)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • 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
Keywords
porcine deltacoronavirus, spike protein, neutralizing antibodies, CD13, receptor binding, epitope mapping, zoonotic coronaviruses, humoral immune response
MeSH terms
Protein Domains, Deltacoronavirus, Animals, Antibodies, Viral, Epitopes, Humans, Protein Binding, Swine, Swine Diseases, Coronavirus Infections, CD13 Antigens, Antibodies, Neutralizing, HEK293 Cells, 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