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SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.

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.

SUBMITTER: Rosa A

PROVIDER: S-EPMC8163077 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.

Rosa Annachiara A Pye Valerie E VE Graham Carl C Muir Luke L Seow Jeffrey J Ng Kevin W KW Cook Nicola J NJ Rees-Spear Chloe C Parker Eleanor E Dos Santos Mariana Silva MS Rosadas Carolina C Susana Alberto A Rhys Hefin H Nans Andrea A Masino Laura L Roustan Chloe C Christodoulou Evangelos E Ulferts Rachel R Wrobel Antoni G AG Short Charlotte-Eve CE Fertleman Michael M Sanders Rogier W RW Heaney Judith J Spyer Moira M Kjær Svend S Riddell Andy A Malim Michael H MH Beale Rupert R MacRae James I JI Taylor Graham P GP Nastouli Eleni E van Gils Marit J MJ Rosenthal Peter B PB Pizzato Massimo M McClure Myra O MO Tedder Richard S RS Kassiotis George G McCoy Laura E LE Doores Katie J KJ Cherepanov Peter P

Science advances 20210528 22

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 ...[more]

PMID: 33888467

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SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.

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SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity.

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