小柯机器人

美国范德堡大学James E. Crowe等研究人员合作发现，识别刺突蛋白N末端结构域的人类单克隆抗体对SARS-CoV-2具有中和性 。该项研究成果于2021年3月16日在线发表在《细胞》杂志上。

研究人员表示，大多数中和SARS-CoV-2的人类单克隆抗体（mAbs）均能识别刺突（S）蛋白受体结合域，并阻断病毒与细胞受体血管紧张素转化酶2的相互作用。

研究人员报道了一组人类单克隆抗体，这些抗体与SARS-CoV-2恢复期供体的S蛋白的N末端域（NTD）上的多种表位结合，并发现其中的少数具有中和活性。两个单克隆抗体（COV2-2676和COV2-2489）抑制了真实SARS-CoV-2和重组VSV/SARS-CoV-2病毒的感染。研究人员通过丙氨酸筛选诱变和功能性SARS-CoV-2 S中和逃逸变体的选择来绘制它们的结合表位。

机理研究表明，这些抗体通过抑制感染周期中的结合后步骤而部分中和。COV2-2676和COV2-2489提供预防或治疗方面的保护，并且需要Fc效应子功能才能获得最佳保护。因此，自然感染诱导了有效的NTD特异性mAb亚群，进而利用中和与Fc介导的活性来防御SARS-CoV-2感染。

附：英文原文

Title: Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein

Author: Naveenchandra Suryadevara, Swathi Shrihari, Pavlo Gilchuk, Laura A. VanBlargan, Elad Binshtein, Seth J. Zost, Rachel S. Nargi, Rachel E. Sutton, Emma S. Winkler, Elaine C. Chen, Mallorie E. Fouch, Edgar Davidson, Benjamin J. Doranz, Rita E. Chen, Pei-Yong Shi, Robert H. Carnahan, Larissa B. Thackray, Michael S. Diamond, James E. Crowe

Issue&Volume: 2021-03-16

Abstract: Most human monoclonal antibodies (mAbs) neutralizing SARS-CoV-2 recognize the spike (S) protein receptor-binding domain and block virus interactions with the cellular receptor angiotensin-converting enzyme 2. We describe a panel of human mAbs binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity. Two mAbs (COV2-2676 and COV2-2489) inhibited infection of authentic SARS-CoV-2 and recombinant VSV/SARS-CoV-2 viruses. We mapped their binding epitopes by alanine-scanning mutagenesis and selection of functional SARS-CoV-2 S neutralization escape variants. Mechanistic studies showed that these antibodies neutralize in part by inhibiting a post-attachment step in the infection cycle. COV2-2676 and COV2-2489 offered protection either as prophylaxis or therapy, and Fc effector functions were required for optimal protection. Thus, natural infection induces a subset of potent NTD-specific mAbs that leverage neutralizing and Fc-mediated activities to protect against SARS-CoV-2 infection using multiple functional attributes.

DOI: 10.1016/j.cell.2021.03.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00357-3