Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants.
Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants.
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DOI：
10.1016/j.jmb.2021.167058
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发表时间：
2021-07-23
影响因子：
5.6
通讯作者：
Lebbink JHG
中科院分区：
文献类型：
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作者：
Laffeber C;de Koning K;Kanaar R;Lebbink JHG
迅速传播的SARS-CoV-2新变种携带病毒刺突蛋白的多个突变，该蛋白附着在宿主细胞上的血管紧张素转换酶2（ACE 2）受体上。这些突变包括N501 Y（谱系B.1.1.7，首次在英国发现）和N501 Y、E484 K、K417 N（B.1.351，首次在南非发现）的组合，所有这些突变都位于受体结合结构域（RBD）的界面。我们通过实验确定，含有N501 Y突变的RBD与hACE 2受体的结合比野生型RBD强7倍。E484 K突变仅略微增强对受体的亲和力，而K417 N减弱亲和力。因此，来自含有所有三个突变的B.1.351的RBD与hACE 2的结合比野生型RBD强3倍，但比N501 Y弱2倍。然而，最近出现的双突变体E484 K/N501 Y的结合甚至比N501 Y更强。含有对受体结合亲和力、病毒传播和免疫逃避具有不同影响的突变的谱系的独立进化强调了全球病毒基因组监测和功能表征的重要性。
Rapidly spreading new variants of SARS-CoV-2 carry multiple mutations in the viral spike protein which attaches to the angiotensin converting enzyme 2 (ACE2) receptor on host cells. Among these mutations are amino acid changes N501Y (lineage B.1.1.7, first identified in the UK), and the combination N501Y, E484K, K417N (B.1.351, first identified in South Africa), all located at the interface on the receptor binding domain (RBD). We experimentally establish that RBD containing the N501Y mutation results in 7-fold stronger binding to the hACE2 receptor than wild type RBD. The E484K mutation only slightly enhances the affinity for the receptor, while K417N attenuates affinity. As a result, RBD from B.1.351 containing all three mutations binds 3-fold stronger to hACE2 than wild type RBD but 2-fold weaker than N501Y. However, the recently emerging double mutant E484K/N501Y binds even stronger than N501Y. The independent evolution of lineages containing mutations with different effects on receptor binding affinity, viral transmission and immune evasion underscores the importance of global viral genome surveillance and functional characterization.
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影响因子：
11.8
作者：
Nonaka CKV;Franco MM;Gräf T;de Lorenzo Barcia CA;de Ávila Mendonça RN;de Sousa KAF;Neiva LMC;Fosenca V;Mendes AVA;de Aguiar RS;Giovanetti M;de Freitas Souza BS
通讯作者：
de Freitas Souza BS
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
影响因子：
64.5
作者：
Thomson EC;Rosen LE;Shepherd JG;Spreafico R;da Silva Filipe A;Wojcechowskyj JA;Davis C;Piccoli L;Pascall DJ;Dillen J;Lytras S;Czudnochowski N;Shah R;Meury M;Jesudason N;De Marco A;Li K;Bassi J;O'Toole A;Pinto D;Colquhoun RM;Culap K;Jackson B;Zatta F;Rambaut A;Jaconi S;Sreenu VB;Nix J;Zhang I;Jarrett RF;Glass WG;Beltramello M;Nomikou K;Pizzuto M;Tong L;Cameroni E;Croll TI;Johnson N;Di Iulio J;Wickenhagen A;Ceschi A;Harbison AM;Mair D;Ferrari P;Smollett K;Sallusto F;Carmichael S;Garzoni C;Nichols J;Galli M;Hughes J;Riva A;Ho A;Schiuma M;Semple MG;Openshaw PJM;Fadda E;Baillie JK;Chodera JD;ISARIC4C Investigators;COVID-19 Genomics UK (COG-UK) Consortium;Rihn SJ;Lycett SJ;Virgin HW;Telenti A;Corti D;Robertson DL;Snell G
通讯作者：
Snell G
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.