SARS-CoV-2 spike protein: a key target for eliciting persistent neutralizing antibodies.
SARS-CoV-2 spike protein: a key target for eliciting persistent neutralizing antibodies.
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DOI：
10.1038/s41392-021-00523-5
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发表时间：
2021-02-26
影响因子：
39.3
通讯作者：
Du L
中科院分区：
文献类型：
--
作者：
Yang Y;Du L
最近发表在《科学》杂志上的一篇论文描述了对严重急性呼吸道综合征冠状病毒（SARS-CoV-2）感染个体的IgG抗体反应的检测。作者还检查了抗体产生的持续时间以及IgG抗体滴度与中和抗体滴度之间的相关性。1这项研究提供了关于2019冠状病毒病（COVID-19）患者抗体产生动力学以及这些抗体的功能和寿命的信息。SARS-CoV-2基因组编码刺突（S）、核衣壳、膜和包膜结构蛋白。S蛋白在病毒感染和致病中起关键作用。2它包括亚基S1和S2：S1含有N-末端结构域（NTD）和受体结合结构域（RBD），而S2含有七肽重复序列1（HR 1）和HR 2（图1a）。SARS-CoV-2感染经历一系列过程：RBD首先与其受体血管紧张素转换酶2（ACE 2）结合，形成RBD/ACE 2复合物。这引发S蛋白的构象变化，导致通过HR 1和HR 2介导的膜融合;该过程最终导致病毒进入靶细胞（图1 B）。与其他结构蛋白不同，S蛋白是诱导SARS-CoV-2特异性抗体，特别是中和抗体的关键靶标。针对S蛋白不同区域的抗体抑制SARS-CoV-2感染的机制不同。例如，NTD靶向抗体（单克隆抗体（mAb）或其片段）与NTD结合形成NTD/mAb复合物，从而阻止S蛋白的构象变化并阻断膜融合和病毒进入（图1 B）。相比之下，RBD靶向抗体如mAb和纳米抗体（Nbs）形成RBD/mAb或RBD/Nb复合物，其抑制RBD与ACE 2的结合，从而防止SARS-CoV-2进入靶细胞（图1 B）。因此，了解上述SARS-CoV-2感染的机制和抗SARS-CoV-2-S抗体的作用模式将有助于阐明SARS-CoV-2感染个体中抗体产生的动力学，并促进有效对策的发展。一般来说，针对病毒RBD的抗体比针对S蛋白其他区域（如NTD）的抗体更有效，但它们在抑制多种病毒株方面可能不那么广泛。科学论文显示，抗SARS-CoV-2-S抗体在感染后以可检测的滴度被激发。1作者检测了轻度至中度COVID-19症状患者恢复期血浆中的IgG抗体。他们用稳定的SARS-CoV-2S三聚体蛋白包被平板进行ELISA。
A recent paper published in Science describes the detection of IgG antibody responses in individuals infected by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The authors also examined the duration of antibody production and the correlation between IgG antibody titers and neutralizing antibody titers. 1 This study provides information about the kinetics of antibody production, and the functionality and longevity of these antibodies, in patients with Coronavirus Disease 2019 (COVID-19). The SARS-CoV-2 genome encodes spike (S), nucleocapsid, membrane, and envelope structural proteins. The S protein plays a key role in viral infection and pathogenesis. 2 It comprises subunits S1 and S2: S1 harbors the N-terminal domain (NTD) and the receptor-binding domain (RBD), whereas S2 harbors heptad repeat 1 (HR1) and HR2 (Fig. 1 a). SARS-CoV-2 infection undergoes a series of processes: the RBD first binds its receptor, angiotensin converting enzyme 2 (ACE2), to form an RBD/ACE2 complex. This triggers conformational changes in the S protein, leading to membrane fusion mediated via HR1 and HR2; this process culminates in viral entry into target cells (Fig. 1 b). Different from other structural proteins, the S protein is a critical target for the induction of antibodies, particularly neutralizing antibodies, specific for SARS-CoV-2. Antibodies targeting various regions of S protein have different mechanisms in inhibiting SARS-CoV-2 infection. For example, NTD-targeting antibodies (monoclonal antibodies (mAbs) or their fragments) bind the NTD to form an NTD/mAb complex, thereby preventing conformational changes in the S protein and blocking membrane fusion and viral entry (Fig. 1 b). By contrast, RBD-targeting antibodies such as mAbs and nanobodies (Nbs) form RBD/mAb or RBD/Nb complexes that inhibit binding of the RBD to ACE2, thereby preventing entry of SARS-CoV-2 into target cells (Fig. 1 b). Thus, understanding the aforementioned mechanism underlying SARS-CoV-2 infection and the mode of action of anti-SARS-CoV-2-S antibodies will help elucidate the kinetics of antibody production in SARS-CoV-2-infected individuals, and facilitate the development of effective countermeasures. In general, antibodies targeting the viral RBD are more potent than the antibodies targeting other regions (such as NTD) of S protein, but they might be less broad in inhibiting multiple virus strains.The Science paper shows that anti-SARS-CoV-2-S antibodies are elicited at detectable titers after infection. 1 The authors detected IgG antibodies in convalescent plasma from patients with mild-tomoderate COVID-19 symptoms. They performed an ELISA by coating plates with a stabilized SARS-CoV-2 S trimer protein.
人类抗体对SARS-COV-2峰值蛋白的受体结合结构域的持久性和衰减在COVID-19患者中。
影响因子：
24.8
作者：
Iyer AS;Jones FK;Nodoushani A;Kelly M;Becker M;Slater D;Mills R;Teng E;Kamruzzaman M;Garcia-Beltran WF;Astudillo M;Yang D;Miller TE;Oliver E;Fischinger S;Atyeo C;Iafrate AJ;Calderwood SB;Lauer SA;Yu J;Li Z;Feldman J;Hauser BM;Caradonna TM;Branda JA;Turbett SE;LaRocque RC;Mellon G;Barouch DH;Schmidt AG;Azman AS;Alter G;Ryan ET;Harris JB;Charles RC
通讯作者：
Charles RC
DOI：
10.1126/science.abd7728
发表时间：
2020-12-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Wajnberg A;Amanat F;Firpo A;Altman DR;Bailey MJ;Mansour M;McMahon M;Meade P;Mendu DR;Muellers K;Stadlbauer D;Stone K;Strohmeier S;Simon V;Aberg J;Reich DL;Krammer F;Cordon-Cardo C
通讯作者：
Cordon-Cardo C
影响因子：
15.9
作者：
Salazar, Eric;Kuchipudi, Suresh V.;Musser, James M.
通讯作者：
Musser, James M.