SARS-CoV-2 can recruit a haem metabolite to evade antibody immunity
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Annachiara Rosa Val Pye Carl Graham Luke Muir Jeffrey Seow Kevin Ng Nicola 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 Kjaer Andy Riddell Michael H Malim Rupert Beale James Macrae Graham P Taylor Eleni Nastouli Marit J van Gils Peter Rosenthal Massimo Pizzato Myra O McClure Richard S Tedder George Kassiotis Laura E Mccoy Katie J Doores Peter Cherepanov Toggle all authors (40)
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.
Journal details
Journal Science advances
Volume 7
Issue number 22
Pages eabg7607
Available online
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Publisher website (DOI) 10.1126/sciadv.abg7607
Figshare View on figshare
Europe PubMed Central 33888467
Pubmed 33888467
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