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Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.
Sankhala, Rajeshwer S; Dussupt, Vincent; Chen, Wei-Hung; Bai, Hongjun; Martinez, Elizabeth J; Jensen, Jaime L; Rees, Phyllis A; Hajduczki, Agnes; Chang, William C; Choe, Misook; Yan, Lianying; Sterling, Spencer L; Swafford, Isabella; Kuklis, Caitlin; Soman, Sandrine; King, Jocelyn; Corbitt, Courtney; Zemil, Michelle; Peterson, Caroline E; Mendez-Rivera, Letzibeth; Townsley, Samantha M; Donofrio, Gina C; Lal, Kerri G; Tran, Ursula; Green, Ethan C; Smith, Clayton; de Val, Natalia; Laing, Eric D; Broder, Christopher C; Currier, Jeffrey R; Gromowski, Gregory D; Wieczorek, Lindsay; Rolland, Morgane; Paquin-Proulx, Dominic; van Dyk, Dewald; Britton, Zachary; Rajan, Saravanan; Loo, Yueh Ming; McTamney, Patrick M; Esser, Mark T; Polonis, Victoria R; Michael, Nelson L; Krebs, Shelly J; Modjarrad, Kayvon; Joyce, M Gordon.
Affiliation
  • Sankhala RS; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Dussupt V; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Chen WH; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Bai H; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Martinez EJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Jensen JL; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Rees PA; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Hajduczki A; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Chang WC; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Choe M; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Yan L; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
  • Sterling SL; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
  • Swafford I; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Kuklis C; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Soman S; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • King J; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Corbitt C; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Zemil M; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Peterson CE; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Mendez-Rivera L; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Townsley SM; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Donofrio GC; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Lal KG; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Tran U; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Green EC; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
  • Smith C; Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.
  • de Val N; Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.
  • Laing ED; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
  • Broder CC; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
  • Currier JR; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Gromowski GD; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Wieczorek L; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Rolland M; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Paquin-Proulx D; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • van Dyk D; Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • Britton Z; Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • Rajan S; Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • Loo YM; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • McTamney PM; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • Esser MT; Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
  • Polonis VR; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Michael NL; Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Krebs SJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic
  • Modjarrad K; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Joyce MG; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: gjoyce@eidresearch.org.
Structure ; 32(2): 131-147.e7, 2024 Feb 01.
Article in En | MEDLINE | ID: mdl-38157856
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: En Journal: Structure Journal subject: BIOLOGIA MOLECULAR / BIOQUIMICA / BIOTECNOLOGIA Year: 2024 Document type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Limits: Humans Language: En Journal: Structure Journal subject: BIOLOGIA MOLECULAR / BIOQUIMICA / BIOTECNOLOGIA Year: 2024 Document type: Article Affiliation country: United States