小柯机器人

近日，美国哥伦比亚大学何大一（David D. Ho）等研究人员合作发现靶向SARS-CoV-2突刺蛋白多个表位的强力中和抗体。相关论文于2020年7月22日在线发表于《自然》。

研究人员从5例重症疾病住院患者中分离出61种SARS-CoV-2中和性单克隆抗体。在这些抗体中，有19种在体外有效中和了真实的SARS-CoV-2，其中9种抗体显示出出色的功效，具有0.7至9 ng/mL的50％病毒抑制浓度。表位作图显示，这19种抗体在靶向受体结合域（RBD）的抗体和与N末端域（NTD）的抗体之间平均分配，从而表明这两个均位于病毒突刺顶部的区域是具有免疫原性的。

另外两种强力中和抗体识别与表位顶部结构域重叠的四元表位。一个靶向RBD的抗体，另一个靶向NTD的抗体以及第三个桥接两个单独的RBD抗体的冷冻电子显微镜重建揭示出突刺蛋白的闭合构象。这些单克隆抗体有望作为抗SARS-CoV-2的潜在治疗剂和/或预防剂用于临床开发。

据悉，SARS-CoV-2流行病肆虐，给人类生活和全球经济造成毁灭性后果。发现并开发中和病毒的单克隆抗体可能是治疗或预防这种新型冠状病毒感染的一种方法。

附：英文原文

Title: Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

Author: Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro, David D. Ho

Issue&Volume: 2020-07-22

Abstract: The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

DOI: 10.1038/s41586-020-2571-7

Source: https://www.nature.com/articles/s41586-020-2571-7

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