tetano
Editor, Senior Moderator
Structure
. 2023 Dec 16:S0969-2126(23)00440-9.
doi: 10.1016/j.str.2023.11.015. Online ahead of print. Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain
Rajeshwer S Sankhala[SUP] 1 [/SUP], Vincent Dussupt[SUP] 2 [/SUP], Wei-Hung Chen[SUP] 1 [/SUP], Hongjun Bai[SUP] 2 [/SUP], Elizabeth J Martinez[SUP] 1 [/SUP], Jaime L Jensen[SUP] 1 [/SUP], Phyllis A Rees[SUP] 1 [/SUP], Agnes Hajduczki[SUP] 1 [/SUP], William C Chang[SUP] 1 [/SUP], Misook Choe[SUP] 1 [/SUP], Lianying Yan[SUP] 3 [/SUP], Spencer L Sterling[SUP] 3 [/SUP], Isabella Swafford[SUP] 4 [/SUP], Caitlin Kuklis[SUP] 5 [/SUP], Sandrine Soman[SUP] 5 [/SUP], Jocelyn King[SUP] 5 [/SUP], Courtney Corbitt[SUP] 5 [/SUP], Michelle Zemil[SUP] 4 [/SUP], Caroline E Peterson[SUP] 1 [/SUP], Letzibeth Mendez-Rivera[SUP] 4 [/SUP], Samantha M Townsley[SUP] 4 [/SUP], Gina C Donofrio[SUP] 4 [/SUP], Kerri G Lal[SUP] 2 [/SUP], Ursula Tran[SUP] 4 [/SUP], Ethan C Green[SUP] 3 [/SUP], Clayton Smith[SUP] 6 [/SUP], Natalia de Val[SUP] 6 [/SUP], Eric D Laing[SUP] 3 [/SUP], Christopher C Broder[SUP] 3 [/SUP], Jeffrey R Currier[SUP] 5 [/SUP], Gregory D Gromowski[SUP] 5 [/SUP], Lindsay Wieczorek[SUP] 4 [/SUP], Morgane Rolland[SUP] 2 [/SUP], Dominic Paquin-Proulx[SUP] 4 [/SUP], Dewald van Dyk[SUP] 7 [/SUP], Zachary Britton[SUP] 7 [/SUP], Saravanan Rajan[SUP] 7 [/SUP], Yueh Ming Loo[SUP] 8 [/SUP], Patrick M McTamney[SUP] 8 [/SUP], Mark T Esser[SUP] 8 [/SUP], Victoria R Polonis[SUP] 9 [/SUP], Nelson L Michael[SUP] 10 [/SUP], Shelly J Krebs[SUP] 11 [/SUP], Kayvon Modjarrad[SUP] 12 [/SUP], M Gordon Joyce[SUP] 13 [/SUP]
Affiliations
Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope, and WRAIR-2123, the class I ACE2-binding site. The broad reactivity of class IV and V mAbs to conserved regions of SARS-CoV-2 VoCs and other sarbecovirus provides a framework for long-term immunotherapeutic development strategies.
. 2023 Dec 16:S0969-2126(23)00440-9.
doi: 10.1016/j.str.2023.11.015. Online ahead of print. Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain
Rajeshwer S Sankhala[SUP] 1 [/SUP], Vincent Dussupt[SUP] 2 [/SUP], Wei-Hung Chen[SUP] 1 [/SUP], Hongjun Bai[SUP] 2 [/SUP], Elizabeth J Martinez[SUP] 1 [/SUP], Jaime L Jensen[SUP] 1 [/SUP], Phyllis A Rees[SUP] 1 [/SUP], Agnes Hajduczki[SUP] 1 [/SUP], William C Chang[SUP] 1 [/SUP], Misook Choe[SUP] 1 [/SUP], Lianying Yan[SUP] 3 [/SUP], Spencer L Sterling[SUP] 3 [/SUP], Isabella Swafford[SUP] 4 [/SUP], Caitlin Kuklis[SUP] 5 [/SUP], Sandrine Soman[SUP] 5 [/SUP], Jocelyn King[SUP] 5 [/SUP], Courtney Corbitt[SUP] 5 [/SUP], Michelle Zemil[SUP] 4 [/SUP], Caroline E Peterson[SUP] 1 [/SUP], Letzibeth Mendez-Rivera[SUP] 4 [/SUP], Samantha M Townsley[SUP] 4 [/SUP], Gina C Donofrio[SUP] 4 [/SUP], Kerri G Lal[SUP] 2 [/SUP], Ursula Tran[SUP] 4 [/SUP], Ethan C Green[SUP] 3 [/SUP], Clayton Smith[SUP] 6 [/SUP], Natalia de Val[SUP] 6 [/SUP], Eric D Laing[SUP] 3 [/SUP], Christopher C Broder[SUP] 3 [/SUP], Jeffrey R Currier[SUP] 5 [/SUP], Gregory D Gromowski[SUP] 5 [/SUP], Lindsay Wieczorek[SUP] 4 [/SUP], Morgane Rolland[SUP] 2 [/SUP], Dominic Paquin-Proulx[SUP] 4 [/SUP], Dewald van Dyk[SUP] 7 [/SUP], Zachary Britton[SUP] 7 [/SUP], Saravanan Rajan[SUP] 7 [/SUP], Yueh Ming Loo[SUP] 8 [/SUP], Patrick M McTamney[SUP] 8 [/SUP], Mark T Esser[SUP] 8 [/SUP], Victoria R Polonis[SUP] 9 [/SUP], Nelson L Michael[SUP] 10 [/SUP], Shelly J Krebs[SUP] 11 [/SUP], Kayvon Modjarrad[SUP] 12 [/SUP], M Gordon Joyce[SUP] 13 [/SUP]
Affiliations
- PMID: 38157856
- DOI: 10.1016/j.str.2023.11.015
Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope, and WRAIR-2123, the class I ACE2-binding site. The broad reactivity of class IV and V mAbs to conserved regions of SARS-CoV-2 VoCs and other sarbecovirus provides a framework for long-term immunotherapeutic development strategies.