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Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody
Sanjeev Kumar; Anamika Patel; Lilin Lai; Chennareddy Chakravarthy; Rajesh Valanparambil; Meredith E. Davis-Gardner; Venkata Viswanadh Edara; Susanne Linderman; Elluri Seetharami Reddy; Kamalvishnu Gottimukkala; Kaustuv Nayak; Prashant Bajpai; Vanshika Singh; Filipp Frank; Narayanaiah Cheedarla; Hans Verkerke; Andrew S. Neish; John D. Roback; Grace Mantus; Pawan Kumar Goel; Manju Rahi; Carl W. Davis; Jens Wrammert; Mehul S. Suthar; Rafi Ahmed; Eric Ortlund; Amit Sharma; Kaja Murali Krishna; Anmol Chandele.
Afiliación
  • Sanjeev Kumar; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
  • Anamika Patel; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Lilin Lai; Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
  • Chennareddy Chakravarthy; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University
  • Rajesh Valanparambil; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University
  • Meredith E. Davis-Gardner; Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
  • Venkata Viswanadh Edara; Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
  • Susanne Linderman; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University
  • Elluri Seetharami Reddy; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India; Kusuma School of Biological Sciences, Indi
  • Kamalvishnu Gottimukkala; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
  • Kaustuv Nayak; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
  • Prashant Bajpai; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
  • Vanshika Singh; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
  • Filipp Frank; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Narayanaiah Cheedarla; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Hans Verkerke; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pathology, Brigham and Womens Hospit
  • Andrew S. Neish; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
  • John D. Roback; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Grace Mantus; Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 303
  • Pawan Kumar Goel; Shaheed Hasan Khan Mewat Government Medical College, Haryana, India
  • Manju Rahi; Division of Epidemiology and Communicable Diseases, Indian Council of Medical Research, New Delhi, 110029, India
  • Carl W. Davis; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University
  • Jens Wrammert; Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University, Atlanta, GA 303
  • Mehul S. Suthar; Department of Pediatrics, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA
  • Rafi Ahmed; Department of Microbiology and Immunology, Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University
  • Eric Ortlund; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Amit Sharma; ICMR-National Institute of Malaria Research, Dwarka, New Delhi, 110077, India; Structural Parasitology Group, International Center for Genetic Engineering and B
  • Kaja Murali Krishna; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India; Emory Vaccine Center and Department of Ped
  • Anmol Chandele; ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, New Delhi, 110067, India
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-491770
ABSTRACT
The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor-binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 g/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Idioma: En Año: 2022 Tipo del documento: Preprint