tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2021 Nov 26;1-34.
doi: 10.1080/22221751.2021.2011623. Online ahead of print.
A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses
Pengfei Wang[SUP] 1 [/SUP], Ryan G Casner[SUP] 2 [/SUP], Manoj S Nair[SUP] 1 [/SUP], Jian Yu[SUP] 1 [/SUP], Yicheng Guo[SUP] 1 [/SUP], Maple Wang[SUP] 1 [/SUP], Jasper F-W Chan[SUP] 3 4 [/SUP], Gabriele Cerutti[SUP] 2 [/SUP], Sho Iketani[SUP] 1 [/SUP], Lihong Liu[SUP] 1 [/SUP], Zizhang Sheng[SUP] 1 [/SUP], Zhiwei Chen[SUP] 3 4 [/SUP], Kwok-Yung Yuen[SUP] 3 4 [/SUP], Peter D Kwong[SUP] 2 5 [/SUP], Yaoxing Huang[SUP] 1 [/SUP], Lawrence Shapiro[SUP] 1 2 [/SUP], David D Ho[SUP] 1 6 7 [/SUP]
Affiliations
Abstract
The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.
. 2021 Nov 26;1-34.
doi: 10.1080/22221751.2021.2011623. Online ahead of print.
A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses
Pengfei Wang[SUP] 1 [/SUP], Ryan G Casner[SUP] 2 [/SUP], Manoj S Nair[SUP] 1 [/SUP], Jian Yu[SUP] 1 [/SUP], Yicheng Guo[SUP] 1 [/SUP], Maple Wang[SUP] 1 [/SUP], Jasper F-W Chan[SUP] 3 4 [/SUP], Gabriele Cerutti[SUP] 2 [/SUP], Sho Iketani[SUP] 1 [/SUP], Lihong Liu[SUP] 1 [/SUP], Zizhang Sheng[SUP] 1 [/SUP], Zhiwei Chen[SUP] 3 4 [/SUP], Kwok-Yung Yuen[SUP] 3 4 [/SUP], Peter D Kwong[SUP] 2 5 [/SUP], Yaoxing Huang[SUP] 1 [/SUP], Lawrence Shapiro[SUP] 1 2 [/SUP], David D Ho[SUP] 1 6 7 [/SUP]
Affiliations
- PMID: 34836485
- DOI: 10.1080/22221751.2021.2011623
Abstract
The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.