tetano
Editor, Senior Moderator
MAbs
. Jan-Dec 2022;14(1):2021601.
doi: 10.1080/19420862.2021.2021601.
Computational design of a neutralizing antibody with picomolar binding affinity for all concerning SARS-CoV-2 variants
Bo-Seong Jeong[SUP] 1 [/SUP], Jeong Seok Cha[SUP] 2 [/SUP], Insu Hwang[SUP] 3 [/SUP], Uijin Kim[SUP] 2 [/SUP], Jared Adolf-Bryfogle[SUP] 4 5 [/SUP], Brian Coventry[SUP] 6 [/SUP], Hyun-Soo Cho[SUP] 2 [/SUP], Kyun-Do Kim[SUP] 3 [/SUP], Byung-Ha Oh[SUP] 1 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019, caused by SARS-CoV-2, remains an on-going pandemic, partly due to the emergence of variant viruses that can "break-through" the protection of the current vaccines and neutralizing antibodies (nAbs), highlighting the needs for broadly nAbs and next-generation vaccines. We report an antibody that exhibits breadth and potency in binding the receptor-binding domain (RBD) of the virus spike glycoprotein across SARS coronaviruses. Initially, a lead antibody was computationally discovered and crystallographically validated that binds to a highly conserved surface of the RBD of wild-type SARS-CoV-2. Subsequently, through experimental affinity enhancement and computational affinity maturation, it was further developed to bind the RBD of all concerning SARS-CoV-2 variants, SARS-CoV-1 and pangolin coronavirus with pico-molar binding affinities, consistently exhibited strong neutralization activity against wild-type SARS-CoV-2 and the Alpha and Delta variants. These results identify a vulnerable target site on coronaviruses for development of pan-sarbecovirus nAbs and vaccines.
Keywords: Computational antibody discovery; Sars-CoV-2; broad-spectrum vaccine; broadly neutralizing antibody; emerging variants.
. Jan-Dec 2022;14(1):2021601.
doi: 10.1080/19420862.2021.2021601.
Computational design of a neutralizing antibody with picomolar binding affinity for all concerning SARS-CoV-2 variants
Bo-Seong Jeong[SUP] 1 [/SUP], Jeong Seok Cha[SUP] 2 [/SUP], Insu Hwang[SUP] 3 [/SUP], Uijin Kim[SUP] 2 [/SUP], Jared Adolf-Bryfogle[SUP] 4 5 [/SUP], Brian Coventry[SUP] 6 [/SUP], Hyun-Soo Cho[SUP] 2 [/SUP], Kyun-Do Kim[SUP] 3 [/SUP], Byung-Ha Oh[SUP] 1 [/SUP]
Affiliations
- PMID: 35030983
- DOI: 10.1080/19420862.2021.2021601
Abstract
Coronavirus disease 2019, caused by SARS-CoV-2, remains an on-going pandemic, partly due to the emergence of variant viruses that can "break-through" the protection of the current vaccines and neutralizing antibodies (nAbs), highlighting the needs for broadly nAbs and next-generation vaccines. We report an antibody that exhibits breadth and potency in binding the receptor-binding domain (RBD) of the virus spike glycoprotein across SARS coronaviruses. Initially, a lead antibody was computationally discovered and crystallographically validated that binds to a highly conserved surface of the RBD of wild-type SARS-CoV-2. Subsequently, through experimental affinity enhancement and computational affinity maturation, it was further developed to bind the RBD of all concerning SARS-CoV-2 variants, SARS-CoV-1 and pangolin coronavirus with pico-molar binding affinities, consistently exhibited strong neutralization activity against wild-type SARS-CoV-2 and the Alpha and Delta variants. These results identify a vulnerable target site on coronaviruses for development of pan-sarbecovirus nAbs and vaccines.
Keywords: Computational antibody discovery; Sars-CoV-2; broad-spectrum vaccine; broadly neutralizing antibody; emerging variants.