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.
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.
