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SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.
Rosa, Annachiara; Pye, Valerie E; Graham, Carl; Muir, Luke; Seow, Jeffrey; Ng, Kevin W; Cook, Nicola J; Rees-Spear, Chloe; Parker, Eleanor; Dos Santos, Mariana Silva; Rosadas, Carolina; Susana, Alberto; Rhys, Hefin; Nans, Andrea; Masino, Laura; Roustan, Chloe; Christodoulou, Evangelos; Ulferts, Rachel; Wrobel, Antoni G; Short, Charlotte-Eve; Fertleman, Michael; Sanders, Rogier W; Heaney, Judith; Spyer, Moira; Kjær, Svend; Riddell, Andy; Malim, Michael H; Beale, Rupert; MacRae, James I; Taylor, Graham P; Nastouli, Eleni; van Gils, Marit J; Rosenthal, Peter B; Pizzato, Massimo; McClure, Myra O; Tedder, Richard S; Kassiotis, George; McCoy, Laura E; Doores, Katie J; Cherepanov, Peter.
  • Rosa A; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.
  • Pye VE; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.
  • Graham C; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Muir L; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.
  • Seow J; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • Ng KW; Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK.
  • Cook NJ; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.
  • Rees-Spear C; Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.
  • Parker E; Department of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.
  • Dos Santos MS; Metabolomics Science Technology Platform, The Francis Crick Institute, London, UK.
  • Rosadas C; Department of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.
  • Susana A; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
  • Rhys H; Flow Cytometry Science and Technology Platform, The Francis Crick Institute, London, UK.
  • Nans A; Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • Masino L; Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • Roustan C; Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • Christodoulou E; Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • Ulferts R; Cell Biology of Infection Laboratory, The Francis Crick Institute, London, UK.
  • Wrobel AG; Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, London, UK.
  • Short CE; Department of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.
  • Fertleman M; Cutrale Perioperative and Ageing Group, Imperial College London, London, UK.
  • Sanders RW; Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.
  • Heaney J; Weill Medical College of Cornell University, New York, NY, USA.
  • Spyer M; Advanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.
  • Kjær S; Crick COVID-19 Consortium, The Francis Crick Institute, London, UK.
  • Riddell A; Advanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.
  • Malim MH; Crick COVID-19 Consortium, The Francis Crick Institute, London, UK.
  • Beale R; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health.
  • MacRae JI; Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • Taylor GP; Flow Cytometry Science and Technology Platform, The Francis Crick Institute, London, UK.
  • Nastouli E; Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
  • van Gils MJ; Cell Biology of Infection Laboratory, The Francis Crick Institute, London, UK.
  • Rosenthal PB; Metabolomics Science Technology Platform, The Francis Crick Institute, London, UK.
  • Pizzato M; Department of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.
  • McClure MO; Advanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.
  • Tedder RS; Crick COVID-19 Consortium, The Francis Crick Institute, London, UK.
  • Kassiotis G; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health.
  • McCoy LE; Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.
  • Doores KJ; Structural Biology of Cells and Viruses Laboratory, The Francis Crick Institute, London, UK.
  • Cherepanov P; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
Sci Adv ; 7(22)2021 05.
Article in English | MEDLINE | ID: covidwho-1388434
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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Semantic information from SemMedBD (by NLM)
1. Immune Sera INHIBITS Antibodie
Subject
Immune Sera
Predicate
INHIBITS
Object
Antibodie
2. Tetrapyrroles INTERACTS_WITH Epitopes
Subject
Tetrapyrroles
Predicate
INTERACTS_WITH
Object
Epitopes
3. Epitopes INTERACTS_WITH Metabolite
Subject
Epitopes
Predicate
INTERACTS_WITH
Object
Metabolite
4. Immune Sera INHIBITS Antibodies, Neutralizing
Subject
Immune Sera
Predicate
INHIBITS
Object
Antibodies, Neutralizing
5. Tetrapyrroles INTERACTS_WITH Epitopes
Subject
Tetrapyrroles
Predicate
INTERACTS_WITH
Object
Epitopes
6. Epitopes INTERACTS_WITH Metabolite
Subject
Epitopes
Predicate
INTERACTS_WITH
Object
Metabolite
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 heme 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 SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through recruitment of a metabolite.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 / Heme Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: SCIADV.ABG7607

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 / Heme Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: SCIADV.ABG7607