Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.
Epitope Classification and RBD Binding Properties of Neutralizing Antibodies Against SARS-CoV-2 Variants of Concern.
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DOI：
10.3389/fimmu.2021.691715
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发表时间：
2021
影响因子：
7.3
通讯作者：
Walter MR
中科院分区：
文献类型：
--
作者：
Deshpande A;Harris BD;Martinez-Sobrido L;Kobie JJ;Walter MR
严重急性呼吸道综合征冠状病毒-2（SAR-CoV-2）引起2019冠状病毒病（COVID 19），该疾病在易感宿主中造成短期和长期疾病以及死亡。SARS-CoV-2 Spike（S）蛋白的受体结合结构域（RBD）与细胞表面血管紧张素转换酶II型（ACE 2）结合以启动病毒附着并最终启动病毒发病机制。SARS-CoV-2 S RBD是阻断RBD -ACE 2相互作用的中和抗体（NAb）的主要靶标。在本报告中，NAb-RBD结合表位在蛋白质数据库中被分类为C1，C1 D，C2，C3，或C4，使用RBD结合谱（BP），基于NAb特异性RBD掩埋表面积，并用于预测一系列未表征的NAb的结合表位。还定量了天然存在的SARS-CoV-2 RBD序列变异，以预测NAb对RBD变体的结合敏感性。NAb和ACE 2结合研究证实了NAb分类，并确定RBD变体是否增强ACE 2结合以促进病毒感染性，和/或破坏NAb结合以逃避宿主免疫应答。在评价的9种单一RBD突变体中，K417 T、E484 K和N501 Y破坏了65%的评价NAb的结合，这与SARS-CoV-2 P.1日本/巴西毒株作为关注变体（VoC）的分配一致。RBD变体E484 K和N501 Y表现出与武汉-1参考SARS-CoV-2 RBD相当的ACE 2结合。虽然对NAb结合的破坏性稍小，但L452 R增强ACE 2结合亲和力。因此，与SARS-CoV-2加州VoC（B.1.427/B.1.429-加州）相关的L452 R突变体已进化为增强ACE 2结合，同时破坏C1和C2 NAb类。该分析还鉴定了与所有评估的SARS-CoV-2 RBD变体结合的非重叠抗体对（1213 H7和1215 D1），代表了治疗SARS-CoV-2 WT和VoC毒株的极好治疗选择。
Severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) causes coronavirus disease 2019 (COVID19) that is responsible for short and long-term disease, as well as death, in susceptible hosts. The receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) protein binds to cell surface angiotensin converting enzyme type-II (ACE2) to initiate viral attachment and ultimately viral pathogenesis. The SARS-CoV-2 S RBD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 interactions. In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants. NAb and ACE2 binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). RBD variants E484K and N501Y exhibited ACE2 binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. While slightly less disruptive to NAb binding, L452R enhanced ACE2 binding affinity. Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC (B.1.427/B.1.429-California), has evolved to enhance ACE2 binding, while simultaneously disrupting C1 and C2 NAb classes. The analysis also identified a non-overlapping antibody pair (1213H7 and 1215D1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT and VoC strains.
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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
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
影响因子：
32.4
作者：
Liu, Hejun;Wu, Nicholas C;Wilson, Ian A
通讯作者：
Wilson, Ian A
影响因子：
8
作者：
McAndrews, Kathleen M.;Dowlatshahi, Dara P.;Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
56.9
作者：
Lv, Zhe;Deng, Yong-Qiang;Wang, Xiangxi
通讯作者：
Wang, Xiangxi