eprintid: 10127032 rev_number: 23 eprint_status: archive userid: 608 dir: disk0/10/12/70/32 datestamp: 2021-05-05 07:55:32 lastmod: 2022-08-22 13:30:15 status_changed: 2021-05-05 07:55:32 type: article metadata_visibility: show creators_name: Rosa, A creators_name: Pye, VE creators_name: Graham, C creators_name: Muir, L creators_name: Seow, J creators_name: Ng, KW creators_name: Cook, NJ creators_name: Rees-Spear, C creators_name: Parker, E creators_name: Silva Dos Santos, M creators_name: Rosadas, C creators_name: Susana, A creators_name: Rhys, H creators_name: Nans, A creators_name: Masino, L creators_name: Roustan, C creators_name: Christodoulou, E creators_name: Ulferts, R creators_name: Wrobel, AG creators_name: Short, C-E creators_name: Fertleman, M creators_name: Sanders, RW creators_name: Heaney, J creators_name: Spyer, M creators_name: Kjær, S creators_name: Riddell, A creators_name: Malim, MH creators_name: Beale, R creators_name: MacRae, JI creators_name: Taylor, GP creators_name: Nastouli, E creators_name: van Gils, MJ creators_name: Rosenthal, PB creators_name: Pizzato, M creators_name: McClure, MO creators_name: Tedder, RS creators_name: Kassiotis, G creators_name: McCoy, LE creators_name: Doores, KJ creators_name: Cherepanov, P title: SARS-CoV-2 can recruit a haem metabolite to evade antibody immunity. ispublished: inpress subjects: UCH divisions: UCL divisions: B02 divisions: C10 divisions: D15 divisions: D17 divisions: G93 divisions: D13 divisions: G24 note: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY) 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 SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through the recruitment of a metabolite. date: 2021-04-22 date_type: published official_url: https://doi.org/10.1126/sciadv.abg7607 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1860472 doi: 10.1126/sciadv.abg7607 pii: sciadv.abg7607 lyricists_name: Beale, Rupert lyricists_name: McCoy, Laura lyricists_name: Muir, Luke lyricists_name: Nastouli, Eleni lyricists_name: Rees-Spear, Chloe lyricists_name: Spyer, Moira lyricists_id: RBEAL65 lyricists_id: LEFMC71 lyricists_id: LMUIR32 lyricists_id: ENAST37 lyricists_id: CREES12 lyricists_id: MJSPY20 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Science Advances event_location: United States citation: Rosa, A; Pye, VE; Graham, C; Muir, L; Seow, J; Ng, KW; Cook, NJ; ... Cherepanov, P; + view all <#> Rosa, A; Pye, VE; Graham, C; Muir, L; Seow, J; Ng, KW; Cook, NJ; Rees-Spear, C; Parker, E; Silva Dos Santos, M; Rosadas, C; Susana, A; Rhys, H; Nans, A; Masino, L; Roustan, C; Christodoulou, E; Ulferts, R; Wrobel, AG; Short, C-E; 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; - view fewer <#> (2021) SARS-CoV-2 can recruit a haem metabolite to evade antibody immunity. Science Advances 10.1126/sciadv.abg7607 <https://doi.org/10.1126/sciadv.abg7607>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10127032/1/sciadv.abg7607.full.pdf