SARS-CoV-2 强效中和作用的结构基础及抗体亲和力成熟的作用。
Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.
机构信息
Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA.
Division of Infectious Disease, Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA, USA.
出版信息
Nat Commun. 2020 Oct 27;11(1):5413. doi: 10.1038/s41467-020-19231-9.
SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.
严重急性呼吸综合征冠状病毒 2 是一种贝塔冠状病毒，是引发 COVID-19 大流行的病毒。在此，我们确定了从感染 SARS-CoV-2 的患者中分离出的一种强效中和单克隆抗体 CV30 与受体结合域复合物的 X 射线晶体结构。该结构揭示了 CV30 结合到一个表位上，该表位与人类 ACE2 受体结合基序重叠，为其中和作用提供了结构基础。CV30 还诱导 S1 亚基的脱落，表明其具有中和作用的另一种机制。CV30 的种系回复导致其结合亲和力和中和潜力的显著降低，这表明针对 SARS-CoV-2 的强效中和抗体只需要最小的体细胞突变。
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