期刊
EMERGING MICROBES & INFECTIONS
卷 11, 期 1, 页码 147-157出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2021.2011623
关键词
SARS-CoV-2; antibody; variants; sarbecovirus; SARS-CoV
资金
- JPB Foundation
- Brii Biosciences
- Bill and Melinda Gates Foundation
- NIH
- Intramural Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Health@InnoHK, Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region
The development of potent and broad-spectrum antiviral therapeutics and vaccines is crucial in dealing with highly pathogenic human coronaviruses and their evolving variants. Monoclonal antibody 2-36, isolated from COVID-19-convalescent patients, has been found to cross-neutralize SARS-CoV and other coronaviruses. The cryo-EM structure of 2-36 with SARS-CoV-2 and SARS-CoV spike reveals a conserved epitope in the receptor-binding domain (RBD). This antibody can neutralize various SARS-CoV-2 variants, as well as bat and pangolin sarbecoviruses that use human ACE2 as a receptor.
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.
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