tetano
Editor, Senior Moderator
Heliyon
. 2023 Apr;9(4):e15032.
doi: 10.1016/j.heliyon.2023.e15032. Epub 2023 Apr 3.
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[SUP] 1 [/SUP], Wojciech Jankowski[SUP] 1 [/SUP], Rahel Frick[SUP] 2 [/SUP], Simon P Kelow[SUP] 3 4 [/SUP], Joseph H Lubin[SUP] 5 [/SUP], Vijaya Simhadri[SUP] 1 [/SUP], Jared Adolf-Bryfogle[SUP] 6 [/SUP], Sagar D Khare[SUP] 5 7 [/SUP], Roland L Dunbrack Jr[SUP] 3 [/SUP], Jeffrey J Gray[SUP] 2 8 9 10 [/SUP], Zuben E Sauna[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: Computational antibody design; Coronavirus Disease 2019; Diagnostic; Monoclonal antibody therapeutics; Protein engineering.
. 2023 Apr;9(4):e15032.
doi: 10.1016/j.heliyon.2023.e15032. Epub 2023 Apr 3.
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[SUP] 1 [/SUP], Wojciech Jankowski[SUP] 1 [/SUP], Rahel Frick[SUP] 2 [/SUP], Simon P Kelow[SUP] 3 4 [/SUP], Joseph H Lubin[SUP] 5 [/SUP], Vijaya Simhadri[SUP] 1 [/SUP], Jared Adolf-Bryfogle[SUP] 6 [/SUP], Sagar D Khare[SUP] 5 7 [/SUP], Roland L Dunbrack Jr[SUP] 3 [/SUP], Jeffrey J Gray[SUP] 2 8 9 10 [/SUP], Zuben E Sauna[SUP] 1 [/SUP]
Affiliations
- PMID: 37035348
- PMCID: PMC10069166
- DOI: 10.1016/j.heliyon.2023.e15032
Abstract
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.
Keywords: Computational antibody design; Coronavirus Disease 2019; Diagnostic; Monoclonal antibody therapeutics; Protein engineering.