Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2.
Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2.
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SARS-COV-2的受体结合结构域上保守的中和表位的结构基础。
DOI：
10.1038/s41467-023-35949-8
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发表时间：
2023-01-19
影响因子：
16.6
通讯作者：
Ma, Che
中科院分区：
文献类型：
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作者：
Huang, Kuan-Ying A.;Chen, Xiaorui;Mohapatra, Arpita;Nguyen, Hong Thuy Vy;Schimanski, Lisa;Tan, Tiong Kit;Rijal, Pramila;Vester, Susan K. K.;Hills, Rory A. A.;Howarth, Mark;Keeffe, Jennifer R. R.;Cohen, Alexander A. A.;Kakutani, Leesa M. M.;Wu, Yi-Min;Shahed-Al-Mahmud, Md;Chou, Yu-Chi;Bjorkman, Pamela J. J.;Townsend, Alain R. R.;Ma, Che
抗体介导的免疫在抗SARS-CoV-2感染中起着至关重要的作用。我们分离了一组在自然感染和疫苗接种后引起的中和抗受体结合结构域（RBD）抗体，并表明它们识别核心RBD内表面上的免疫原性补丁，该补丁面向内部并隐藏在“向下”状态中。这些抗体广泛中和野生型（武汉-胡-1）SARS-CoV-2，β和δ变体，有些对其他肉瘤病毒有效。我们观察到从RBD内表面的下部到上部的部分重叠的抗体表位的连续体，并且一些抗体向受体结合基序延伸。大多数抗体基本上受到Omicron BA.1、BA.2和BA.4/5 RBD下部的三个突变热点（S371 L/F、S373 P和S375 F）的损害。相比之下，抗体IY-2A诱导该可变区的部分解折叠，并与保守的构象表位相互作用，以耐受所有抗原变异并中和多种肉瘤病毒。这一发现确定抗体识别不限于RBD上的正常表面结构。总之，功能和结构保守的RBD表位的描述突出了COVID-19的潜在疫苗和治疗候选物。一种抗体IY-2A，从一组4类SARS-CoV-2中和抗体中鉴定，该抗体分离自康复期和接种疫苗的个体，靶向并诱导RBD内保守表位的部分解折叠。IY-2A保留了对BA.4/5亚变体的活性，并中和了多种肉瘤病毒。
Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination and showed that they recognize an immunogenic patch on the internal surface of the core RBD, which faces inwards and is hidden in the “down” state. These antibodies broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta and Delta variants and some are effective against other sarbecoviruses. We observed a continuum of partially overlapping antibody epitopes from lower to upper part of the inner face of the RBD and some antibodies extend towards the receptor-binding motif. The majority of antibodies are substantially compromised by three mutational hotspots (S371L/F, S373P and S375F) in the lower part of the Omicron BA.1, BA.2 and BA.4/5 RBD. By contrast, antibody IY-2A induces a partial unfolding of this variable region and interacts with a conserved conformational epitope to tolerate all antigenic variations and neutralize diverse sarbecoviruses as well. This finding establishes that antibody recognition is not limited to the normal surface structures on the RBD. In conclusion, the delineation of functionally and structurally conserved RBD epitopes highlights potential vaccine and therapeutic candidates for COVID-19. An antibody, IY-2A, identified from a panel of class-4 SARS-CoV-2-neutralizing antibodies isolated from convalescent and vaccinated individuals, targets and induces partial unfolding of a conserved epitope within the RBD. IY-2A retains activity against BA.4/5 subvariants and neutralizes diverse sarbecoviruses.
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SARS-COV-2中和抗体的结构洞察力和合成的调节。
影响因子：
64.5
作者：
Asarnow D;Wang B;Lee WH;Hu Y;Huang CW;Faust B;Ng PML;Ngoh EZX;Bohn M;Bulkley D;Pizzorno A;Ary B;Tan HC;Lee CY;Minhat RA;Terrier O;Soh MK;Teo FJ;Yeap YYC;Seah SGK;Chan CEZ;Connelly E;Young NJ;Maurer-Stroh S;Renia L;Hanson BJ;Rosa-Calatrava M;Manglik A;Cheng Y;Craik CS;Wang CI
通讯作者：
Wang CI
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
30.5
作者：
He, Wan-ting;Musharrafieh, Rami;Song, Ge;Dueker, Katharina;Tse, Longping V.;Martinez, David R.;Schafer, Alexandra;Callaghan, Sean;Yong, Peter;Beutler, Nathan;Torres, Jonathan L.;Volk, Reid M.;Zhou, Panpan;Yuan, Meng;Liu, Hejun;Anzanello, Fabio;Capozzola, Tazio;Parren, Mara;Garcia, Elijah;Rawlings, Stephen A.;Smith, Davey M.;Wilson, Ian A.;Safonova, Yana;Ward, Andrew B.;Rogers, Thomas F.;Baric, Ralph S.;Gralinski, Lisa E.;Burton, Dennis R.;Andrabi, Raiees
通讯作者：
Andrabi, Raiees
两种抗体鸡尾酒中和中和的遗传和结构基础。
影响因子：
28.3
作者：
Dong J;Zost SJ;Greaney AJ;Starr TN;Dingens AS;Chen EC;Chen RE;Case JB;Sutton RE;Gilchuk P;Rodriguez J;Armstrong E;Gainza C;Nargi RS;Binshtein E;Xie X;Zhang X;Shi PY;Logue J;Weston S;McGrath ME;Frieman MB;Brady T;Tuffy KM;Bright H;Loo YM;McTamney PM;Esser MT;Carnahan RH;Diamond MS;Bloom JD;Crowe JE Jr
通讯作者：
Crowe JE Jr
影响因子：
17.1
作者：
通讯作者：
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