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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Heliyon, Vol 9, Iss 4, Pp e15032- (2023)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2023.e15032
Popis: 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.
Databáze: Directory of Open Access Journals