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Rosa A, Pye VE, Graham C, et al. SARS-CoV-2 recruits a haem metabolite to evade antibody immunity. medRxiv. 2021;doi: 10.1101/2021.01.21.21249203.
Rosa, A., Pye, V. E., Graham, C., Muir, L., Seow, J., Ng, K. W., Cook, N. J., Rees-Spear, C., Parker, E., Dos Santos, M. S., Rosadas, C., Susana, A., Rhys, H., Nans, A., Masino, L., Roustan, C., Christodoulou, E., Ulferts, R., Wrobel, A., Short, C. E., Fertleman, M., Sanders, R. W., Heaney, J., Spyer, M., Kjær, S., Riddell, A., Malim, M. H., Beale, R., MacRae, J. I., Taylor, G. P., Nastouli, E., van Gils, M. J., Rosenthal, P. B., Pizzato, M., McClure, M. O., Tedder, R. S., Kassiotis, G., McCoy, L. E., Doores, K. J., & Cherepanov, P. (2021). SARS-CoV-2 recruits a haem metabolite to evade antibody immunity. medRxiv : the preprint server for health sciences, . https://doi.org/10.1101/2021.01.21.21249203
Rosa, Annachiara, et al. "SARS-CoV-2 recruits a haem metabolite to evade antibody immunity." medRxiv : the preprint server for health sciences vol. (2021). doi: https://doi.org/10.1101/2021.01.21.21249203
Rosa A, Pye VE, Graham C, Muir L, Seow J, Ng KW, Cook NJ, Rees-Spear C, Parker E, Dos Santos MS, Rosadas C, Susana A, Rhys H, Nans A, Masino L, Roustan C, Christodoulou E, Ulferts R, Wrobel A, Short CE, Fertleman M, Sanders RW, Heaney J, Spyer M, Kjær S, Riddell A, Malim MH, Beale R, MacRae JI, Taylor GP, Nastouli E, van Gils MJ, Rosenthal PB, Pizzato M, McClure MO, Tedder RS, Kassiotis G, McCoy LE, Doores KJ, Cherepanov P. SARS-CoV-2 recruits a haem metabolite to evade antibody immunity. medRxiv. 2021 Jan 26; doi: 10.1101/2021.01.21.21249203. PMID: 33532784; PMCID: PMC7852234.
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medRxiv. 2021 Jan 26; doi: 10.1101/2021.01.21.21249203.

SARS-CoV-2 recruits a haem metabolite to evade antibody immunity.

medRxiv : the preprint server for health sciences

Annachiara Rosa, Valerie E Pye, Carl Graham, Luke Muir, Jeffrey Seow, Kevin W Ng, Nicola J Cook, Chloe Rees-Spear, Eleanor Parker, Mariana Silva Dos Santos, Carolina Rosadas, Alberto Susana, Hefin Rhys, Andrea Nans, Laura Masino, Chloe Roustan, Evangelos Christodoulou, Rachel Ulferts, Antoni Wrobel, Charlotte-Eve Short, Michael Fertleman, Rogier W Sanders, Judith Heaney, Moira Spyer, Svend Kjær, Andy Riddell, Michael H Malim, Rupert Beale, James I MacRae, Graham P Taylor, Eleni Nastouli, Marit J van Gils, Peter B Rosenthal, Massimo Pizzato, Myra O McClure, Richard S Tedder, George Kassiotis, Laura E McCoy, Katie J Doores, Peter Cherepanov

Affiliations

  1. Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.
  2. Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, UK.
  3. Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.
  4. Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK.
  5. Department of Infectious Disease, St-Mary's Campus, Imperial College London, UK.
  6. Metabolomics Science Technology Platform, The Francis Crick Institute, London, UK.
  7. Department of Cellular, Computational and Integrative Biology, University of Trento, Italy.
  8. Flow Cytometry Science and Technology Platform, The Francis Crick Institute, London, UK.
  9. Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  10. Cell Biology of Infection Laboratory, The Francis Crick Institute, London, UK.
  11. Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, London, UK.
  12. Cutrale Perioperative & Ageing Group, Imperial College London, UK.
  13. Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.
  14. Weill Medical College of Cornell University, New York, US.
  15. Advanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.
  16. Crick COVID-19 Consortium, The Francis Crick Institute, London, UK.
  17. Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health.
  18. Structural Biology of Cells and Viruses Laboratory, The Francis Crick Institute, London, UK.

PMID: 33532784 PMCID: PMC7852234 DOI: 10.1101/2021.01.21.21249203

Abstract

The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of haem metabolism, with nanomolar affinity. Using cryo-electron microscopy and X-ray crystallography we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that the virus co-opts the haem metabolite for the evasion of humoral immunity via allosteric shielding of a sensitive epitope and demonstrate the remarkable structural plasticity of the NTD.

References

  1. J Comput Chem. 2004 Oct;25(13):1605-12 - PubMed
  2. Nat Microbiol. 2020 Dec;5(12):1598-1607 - PubMed
  3. Proc Natl Acad Sci U S A. 2021 Sep 7;118(36): - PubMed
  4. Liver Int. 2009 Aug;29(7):1116-24 - PubMed
  5. J Biol Chem. 1990 Sep 15;265(26):15599-605 - PubMed
  6. Science. 2020 Aug 21;369(6506):956-963 - PubMed
  7. Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14 - PubMed
  8. Nat Methods. 2017 Apr;14(4):331-332 - PubMed
  9. Protein Expr Purif. 2020 Oct;174:105686 - PubMed
  10. Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1260-73 - PubMed
  11. Nature. 2020 Dec;588(7838):498-502 - PubMed
  12. Protein Sci. 2018 Jan;27(1):293-315 - PubMed
  13. Science. 2020 Mar 13;367(6483):1260-1263 - PubMed
  14. Structure. 2007 Mar;15(3):267-73 - PubMed
  15. Acta Crystallogr D Struct Biol. 2020 Feb 1;76(Pt 2):94-101 - PubMed
  16. PLoS Pathog. 2020 Sep 24;16(9):e1008817 - PubMed
  17. Arch Biochem Biophys. 1962 Mar;96:465-7 - PubMed
  18. Nat Methods. 2012 Sep;9(9):853-4 - PubMed
  19. Acta Crystallogr D Biol Crystallogr. 2010 Aug;66(Pt 8):889-900 - PubMed
  20. Science. 2020 Dec 11;370(6522):1339-1343 - PubMed
  21. Front Immunol. 2020 Aug 18;11:2063 - PubMed
  22. J Exp Med. 2020 Nov 2;217(11): - PubMed
  23. Nat Commun. 2019 Sep 24;10(1):4328 - PubMed
  24. Acta Crystallogr D Biol Crystallogr. 2006 Oct;62(Pt 10):1243-50 - PubMed
  25. Annu Rev Biophys. 2018 May 20;47:499-523 - PubMed
  26. J Struct Biol. 2016 Jan;193(1):1-12 - PubMed
  27. Nat Methods. 2017 Mar;14(3):290-296 - PubMed
  28. Liver Int. 2020 Jul;40(7):1787-1788 - PubMed
  29. Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21 - PubMed
  30. Science. 2020 Aug 7;369(6504):650-655 - PubMed
  31. Nat Chem Biol. 2018 Nov;14(11):1032-1042 - PubMed
  32. Nature. 2020 Aug;584(7821):450-456 - PubMed
  33. Cell. 2020 Apr 16;181(2):281-292.e6 - PubMed
  34. Annu Rev Virol. 2016 Sep 29;3(1):237-261 - PubMed
  35. Nat Struct Mol Biol. 2020 Oct;27(10):934-941 - PubMed
  36. Sci Adv. 2021 Jan 1;7(1): - PubMed
  37. PLoS One. 2020 Oct 20;15(10):e0240012 - PubMed
  38. Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):531-544 - PubMed
  39. J Mol Biol. 2003 Oct 31;333(4):721-45 - PubMed
  40. Commun Biol. 2021 Jul 15;4(1):874 - PubMed
  41. Nature. 2020 Aug;584(7819):115-119 - PubMed
  42. Hepatology. 2020 Oct;72(4):1169-1176 - PubMed
  43. Immunity. 2018 Feb 20;48(2):339-349.e5 - PubMed
  44. Nat Struct Mol Biol. 2020 Jan;27(1):78-83 - PubMed
  45. Front Med (Lausanne). 2020 Nov 09;7:598870 - PubMed
  46. Nat Struct Mol Biol. 2020 Aug;27(8):763-767 - PubMed
  47. J Virol Methods. 2009 Mar;156(1-2):1-7 - PubMed
  48. BMJ. 2020 Mar 26;368:m1091 - PubMed
  49. Science. 2020 Nov 20;370(6519):950-957 - PubMed
  50. Nat Med. 2020 Oct;26(10):1623-1635 - PubMed
  51. Clin Exp Immunol. 2020 Nov;202(2):162-192 - PubMed
  52. Nature. 2020 Aug;584(7821):443-449 - PubMed
  53. Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32 - PubMed
  54. Nat Commun. 2020 Sep 4;11(1):4420 - PubMed
  55. Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54 - PubMed
  56. Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32 - PubMed
  57. Nature. 2003 Mar 20;422(6929):307-12 - PubMed
  58. J Virol. 2002 Jun;76(12):6332-43 - PubMed
  59. IUCrJ. 2019 Jun 27;6(Pt 4):526-531 - PubMed
  60. Nature. 2020 Dec;588(7839):682-687 - PubMed
  61. Nat Methods. 2020 Sep;17(9):923-927 - PubMed
  62. Nat Biotechnol. 1997 Sep;15(9):871-5 - PubMed
  63. Cell Rep. 2016 Aug 30;16(9):2327-38 - PubMed
  64. Science. 2020 Aug 7;369(6504):643-650 - PubMed
  65. Front Pharmacol. 2019 Jul 24;10:825 - PubMed
  66. J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674 - PubMed

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