One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening.
One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening.
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DOI：
10.1016/j.celrep.2021.109627
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发表时间：
2021-08-31
期刊：
影响因子：
8.8
通讯作者：
Whitehead TA
中科院分区：
文献类型：
--
作者：
Francino-Urdaniz IM;Steiner PJ;Kirby MB;Zhao F;Haas CM;Barman S;Rhodes ER;Leonard AC;Peng L;Sprenger KG;Jardine JG;Whitehead TA
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）刺突（S）逃逸突变体的潜在出现对现有疫苗和中和抗体（nAb）疗法的有效性构成威胁。迫切需要了解抗体/S逃逸突变景观，以先发制人地解决这一威胁。在这里，我们描述了一种快速的方法来确定逃逸突变体的nAbs靶向S受体结合位点。我们鉴定了五种nAb的逃逸突变体，其中三种来自2019年天然冠状病毒病（COVID-19）感染引起的公共种系VH 3 -53。逃逸突变主要定位于RBD上的血管紧张素转换酶2（ACE 2）识别位点的周边，其中K417、D420、Y 421、F486和Q493是显著的热点。我们提供图书馆，方法和软件作为公开可用的社区资源，以加速针对SARS-CoV-2的新治疗策略。Francino-Urdaniz等人描述了一种用于鉴定SARS-CoV-2 S RBD逃逸突变体的深度突变扫描方法。对自然感染引起的五种中和抗体鉴定了逃逸突变体，揭示了ACE 2识别位点周围位置K417、D420、Y 421、F486和Q493处的热点。
The potential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) escape mutants is a threat to the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutation landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site. We identified escape mutants for five nAbs, including three from the public germline class VH3-53 elicited by natural coronavirus disease 2019 (COVID-19) infection. Escape mutations predominantly mapped to the periphery of the angiotensin-converting enzyme 2 (ACE2) recognition site on the RBD with K417, D420, Y421, F486, and Q493 as notable hotspots. We provide libraries, methods, and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2. Francino-Urdaniz et al. describe a deep mutational scanning method to identify escape mutants on SARS-CoV-2 S RBD. Escape mutants were identified for five neutralizing antibodies elicited from natural infection, revealing hotspots at positions K417, D420, Y421, F486, and Q493 at the periphery of the ACE2 recognition site.
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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
BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
2.4
作者：
Medina-Cucurella, Angelica V.;Steiner, Paul J.;Whitehead, Timothy A.
通讯作者：
Whitehead, Timothy A.