Computational design of nanomolar-binding antibodies specific to multiple SARS-CoV-2 variants by engineering a specificity switch of antibody 80R using RosettaAntibodyDesign (RAbD) results in potential generalizable therapeutic antibodies for novel SARS-CoV-2 virus

Nancy E. Hernandez; Wojciech Jankowski; Rahel Frick; Simon P. Kelow; Joseph H. Lubin; Vijaya Simhadri; Jared Adolf-Bryfogle; Sagar D. Khare; Roland L. Dunbrack, Jr.; Jeffrey J. Gray; Zuben E. Sauna

Heliyon (Apr 2023)

Computational design of nanomolar-binding antibodies specific to multiple SARS-CoV-2 variants by engineering a specificity switch of antibody 80R using RosettaAntibodyDesign (RAbD) results in potential generalizable therapeutic antibodies for novel SARS-CoV-2 virus

Nancy E. Hernandez,
Wojciech Jankowski,
Rahel Frick,
Simon P. Kelow,
Joseph H. Lubin,
Vijaya Simhadri,
Jared Adolf-Bryfogle,
Sagar D. Khare,
Roland L. Dunbrack, Jr.,
Jeffrey J. Gray,
Zuben E. Sauna

Affiliations

Nancy E. Hernandez: Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research U.S. FDA, Silver Spring, MD, USA
Wojciech Jankowski: Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research U.S. FDA, Silver Spring, MD, USA
Rahel Frick: Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA
Simon P. Kelow: Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, USA; Dept. of Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, USA
Joseph H. Lubin: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ USA
Vijaya Simhadri: Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research U.S. FDA, Silver Spring, MD, USA
Jared Adolf-Bryfogle: The Institute for Protein Innovation, Boston, MA, USA
Sagar D. Khare: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ USA; Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
Roland L. Dunbrack, Jr.: Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA, USA
Jeffrey J. Gray: Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA
Zuben E. Sauna: Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research U.S. FDA, Silver Spring, MD, USA; Corresponding author.

Journal volume & issue: Vol. 9, no. 4
p. e15032

Abstract

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The human infectious disease COVID-19 caused by the SARS-CoV-2 virus has become a major threat to global public health. Developing a vaccine is the preferred prophylactic response to epidemics and pandemics. However, for individuals who have contracted the disease, the rapid design of antibodies that can target the SARS-CoV-2 virus fulfils a critical need. Further, discovering antibodies that bind multiple variants of SARS-CoV-2 can aid in the development of rapid antigen tests (RATs) which are critical for the identification and isolation of individuals currently carrying COVID-19. Here we provide a proof-of-concept study for the computational design of high-affinity antibodies that bind to multiple variants of the SARS-CoV-2 spike protein using RosettaAntibodyDesign (RAbD). Well characterized antibodies that bind with high affinity to the SARS-CoV-1 (but not SARS-CoV-2) spike protein were used as templates and re-designed to bind the SARS-CoV-2 spike protein with high affinity, resulting in a specificity switch. A panel of designed antibodies were experimentally validated. One design bound to a broad range of variants of concern including the Omicron, Delta, Wuhan, and South African spike protein variants.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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