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鉴定针对 SARS-CoV RBD 的单克隆抗体,这些抗体对 SARS-CoV-2 具有交叉反应性或中和活性。

Identification of SARS-CoV RBD-targeting monoclonal antibodies with cross-reactive or neutralizing activity against SARS-CoV-2.

机构信息

Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA.

Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

出版信息

Antiviral Res. 2020 Jul;179:104820. doi: 10.1016/j.antiviral.2020.104820. Epub 2020 May 13.

Abstract

SARS-CoV-2-caused COVID-19 cases are growing globally, calling for developing effective therapeutics to control the current pandemic. SARS-CoV-2 and SARS-CoV recognize angiotensin-converting enzyme 2 (ACE2) receptor via the receptor-binding domain (RBD). Here, we identified six SARS-CoV RBD-specific neutralizing monoclonal antibodies (nAbs) that cross-reacted with SARS-CoV-2 RBD, two of which, 18F3 and 7B11, neutralized SARS-CoV-2 infection. 18F3 recognized conserved epitopes on SARS-CoV and SARS-CoV-2 RBDs, whereas 7B11 recognized epitopes on SARS-CoV RBD not fully conserved in SARS-CoV-2 RBD. The 18F3-recognizing epitopes on RBD did not overlap with the ACE2-binding sites, whereas those recognized by 7B11 were close to the ACE2-binding sites, explaining why 7B11 could, but 18F3 could not, block SARS-CoV or SARS-CoV-2 RBD binding to ACE2 receptor. Our study provides an alternative approach to prevent SARS-CoV-2 infection using anti-SARS-CoV nAbs.

摘要

SARS-CoV-2 引起的 COVID-19 病例在全球范围内不断增加,这就需要开发有效的治疗方法来控制当前的大流行。SARS-CoV-2 和 SARS-CoV 通过受体结合域(RBD)识别血管紧张素转换酶 2(ACE2)受体。在这里,我们鉴定了六种 SARS-CoV RBD 特异性中和单克隆抗体(nAbs),它们与 SARS-CoV-2 RBD 发生交叉反应,其中两种,18F3 和 7B11,中和了 SARS-CoV-2 感染。18F3 识别 SARS-CoV 和 SARS-CoV-2 RBD 上保守的表位,而 7B11 识别 SARS-CoV RBD 上不完全保守的表位。18F3 在 RBD 上识别的表位与 ACE2 结合位点不重叠,而 7B11 识别的表位靠近 ACE2 结合位点,这解释了为什么 7B11 可以,但 18F3 不能,阻止 SARS-CoV 或 SARS-CoV-2 RBD 与 ACE2 受体结合。我们的研究提供了一种使用抗 SARS-CoV nAbs 预防 SARS-CoV-2 感染的替代方法。

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