ArticleScience advances2021
SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.
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Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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92citing papers in PubMed
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92 citing papers in PubMed, 156 citations in OpenAlex.
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- Insertion outside the supersite in the N-terminal domain of the SARS-CoV-2 spike glycoprotein may contribute to evasion of neutralizing antibodies.Frontiers in microbiology · 2026Article
- Applications of Pseudoviruses Bearing Glycoproteins of SARS-CoV-2 and Influenza Virus.Advances in experimental medicine and biology · 2026Review
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- Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV.The Journal of clinical investigation · 2024Article
- Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain.Signal transduction and targeted therapy · 2024Article
- Variation in structural motifs within SARS-related coronavirus spike proteins.PLoS pathogens · 2024Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
40 authors at 9 institutions in 4 countries.
Annachiara RosaChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0001-7433-6357
Valerie E PyeChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0001-9616-2992
Carl GrahamDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
Luke MuirInstitute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.ORCID 0000-0002-7834-6066
Jeffrey SeowDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.ORCID 0000-0003-0722-8561
Kevin W NgRetroviral Immunology Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0003-1635-6768
Nicola J CookChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-2738-7976
Chloe Rees-SpearInstitute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.ORCID 0000-0002-7300-2432
Eleanor ParkerDepartment of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.
Mariana Silva Dos SantosMetabolomics Science Technology Platform, The Francis Crick Institute, London, UK.ORCID 0000-0003-2404-8490
Carolina RosadasDepartment of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.ORCID 0000-0002-3922-5667
Alberto SusanaDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
Hefin RhysFlow Cytometry Science and Technology Platform, The Francis Crick Institute, London, UK.
Andrea NansStructural Biology Science Technology Platform, The Francis Crick Institute, London, UK.ORCID 0000-0002-3791-2447
Laura MasinoStructural Biology Science Technology Platform, The Francis Crick Institute, London, UK.ORCID 0000-0002-5326-7003
Chloe RoustanStructural Biology Science Technology Platform, The Francis Crick Institute, London, UK.ORCID 0000-0002-8439-8997
Evangelos ChristodoulouStructural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
Rachel UlfertsCell Biology of Infection Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-4810-9115
Antoni G WrobelStructural Biology of Disease Processes Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-6680-5587
Charlotte-Eve ShortDepartment of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.ORCID 0000-0002-4974-8824
Michael FertlemanCutrale Perioperative and Ageing Group, Imperial College London, London, UK.ORCID 0000-0003-4023-1156
Rogier W SandersDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.ORCID 0000-0002-2324-8573
Judith HeaneyAdvanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.
Moira SpyerAdvanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.ORCID 0000-0001-9149-6029
Svend KjærStructural Biology Science Technology Platform, The Francis Crick Institute, London, UK.ORCID 0000-0001-9767-8683
Andy RiddellFlow Cytometry Science and Technology Platform, The Francis Crick Institute, London, UK.
Michael H MalimDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
Rupert BealeCell Biology of Infection Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-6705-8560
James I MacRaeMetabolomics Science Technology Platform, The Francis Crick Institute, London, UK.ORCID 0000-0002-1464-8583
Graham P TaylorDepartment of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.ORCID 0000-0002-3773-2390
Eleni NastouliAdvanced Pathogen Diagnostic Unit, University College London Hospitals NHS Foundation Trust, London, UK.
Marit J van GilsDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.ORCID 0000-0003-3422-8161
Peter B RosenthalStructural Biology of Cells and Viruses Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-0387-2862
Massimo PizzatoDepartment of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.ORCID 0000-0002-9491-1483
Myra O McClureDepartment of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.
Richard S TedderDepartment of Infectious Disease, St. Mary's Campus, Imperial College London, London, UK.ORCID 0000-0002-9672-5721
George KassiotisRetroviral Immunology Laboratory, The Francis Crick Institute, London, UK. peter.cherepanov@crick.ac.uk katie.doores@kcl.ac.uk l.mccoy@ucl.ac.uk george.kassiotis@crick.ac.uk.ORCID 0000-0002-8457-2633
Laura E McCoyInstitute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK. peter.cherepanov@crick.ac.uk katie.doores@kcl.ac.uk l.mccoy@ucl.ac.uk george.kassiotis@crick.ac.uk.ORCID 0000-0001-9503-7946
Katie J DooresDepartment of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK. peter.cherepanov@crick.ac.uk katie.doores@kcl.ac.uk l.mccoy@ucl.ac.uk george.kassiotis@crick.ac.uk.ORCID 0000-0002-5507-1725
Peter CherepanovChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, UK. peter.cherepanov@crick.ac.uk katie.doores@kcl.ac.uk l.mccoy@ucl.ac.uk george.kassiotis@crick.ac.uk.ORCID 0000-0002-0634-538X
The Francis Crick Institute · GBSt Mary's Hospital · GBKing's College London · GBUniversity College London · GBUniversity College London Hospitals NHS Foundation Trust · GBUniversity of Trento · ITAmsterdam University Medical Centers · NLCornell University · USImperial College London · GB
Funding
Technology Development 2: MAS NMR and dynamic nuclear polarization for HIV-1 structural biologyP50AI150481 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRONENBORN, ANGELA M. · 2019 to 2021
$14.1MCancer Research UK FC001061Medical Research Council MC_PC_19078Medical Research Council MR/R008698/1NIAID NIH HHS P50 AI150481Wellcome Trust 208354/Z/17/ZWellcome Trust FC001061Wellcome Trust FC001065Wellcome Trust FC001078Wellcome Trust FC001099Wellcome Trust FC001827
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.
Indexed as
Antibodies, MonoclonalAntibodies, NeutralizingBilirubinBiliverdineCOVID-19Cryoelectron MicroscopyCrystallography, X-RayEpitopesHemeHumansImmune SeraSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, MonoclonalAntibodies, NeutralizingBilirubinBiliverdineEpitopesHemeImmune SeraSpike Glycoprotein, Coronavirusspike glycoprotein, SARS-CoVspike protein, SARS-CoV-2
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.