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-Structure paper
Title | A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses. |
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Journal, issue, pages | Emerg Microbes Infect, Vol. 11, Issue 1, Page 147-157, Year 2022 |
Publish date | Jan 3, 2022 |
Authors | Pengfei Wang / Ryan G Casner / Manoj S Nair / Jian Yu / Yicheng Guo / Maple Wang / Jasper F-W Chan / Gabriele Cerutti / Sho Iketani / Lihong Liu / Zizhang Sheng / Zhiwei Chen / Kwok-Yung Yuen / Peter D Kwong / Yaoxing Huang / Lawrence Shapiro / David D Ho / |
PubMed 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 ...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 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. |
External links | Emerg Microbes Infect / PubMed:34836485 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.24 Å |
Structure data | EMDB-24190, PDB-7n5h: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Viral Spike / Trimer / Glycoprotein / Neutralizing Antibody Fab / VIRAL PROTEIN-IMMUNE SYSTEM complex |