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一种能够中和 SARS-CoV-2 变体、SARS-CoV 和其他沙贝科病毒的单克隆抗体。

A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses.

机构信息

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.

出版信息

Emerg Microbes Infect. 2022 Dec;11(1):147-157. doi: 10.1080/22221751.2021.2011623.

DOI:10.1080/22221751.2021.2011623
PMID:34836485
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8725896/
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 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.

摘要

高致病性人类冠状病毒的反复出现及其不断进化的变异凸显了开发强效广谱抗病毒治疗药物和疫苗的必要性。通过对从 COVID-19 康复患者中分离出的单克隆抗体（mAbs）进行筛选，我们发现了一种名为 2-36 的 mAb，它对 SARS-CoV 具有交叉中和活性。我们解析了 2-36 与 SARS-CoV-2 或 SARS-CoV 刺突蛋白复合物的冷冻电镜结构，揭示了受体结合域（RBD）中一个高度保守的表位。抗体 2-36 不仅中和了所有当前流行的 SARS-CoV-2 变体和 SARS-CoV，还中和了一组可使用人血管紧张素转化酶 2（ACE2）作为受体的蝙蝠和穿山甲沙贝科病毒。我们选择了 2-36 逃逸病毒，并证实 SARS-CoV-2 RBD 中的 K378T 导致了病毒耐药性。综上所述，2-36 代表了一种用于预防和治疗可能由新发 SARS 相关冠状病毒引起的疾病的战略储备候选药物。其表位为开发泛沙贝科病毒疫苗提供了一个有前景的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/8627e1bbd9fe/TEMI_A_2011623_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/205e957c4907/TEMI_A_2011623_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/672c7279f287/TEMI_A_2011623_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/82fd76f827f9/TEMI_A_2011623_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/8627e1bbd9fe/TEMI_A_2011623_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/205e957c4907/TEMI_A_2011623_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/672c7279f287/TEMI_A_2011623_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/82fd76f827f9/TEMI_A_2011623_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fd9/8725896/8627e1bbd9fe/TEMI_A_2011623_F0004_OC.jpg

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