Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern

被引：0

作者：

Li, Wenwe ^{[1
]}

Chen, Yaozong ^{[2
]}

Prevost, Jeemie ^{[3
,4
]}

Ullah, Irfan ^{[5
]}

Lu, Maoli ^{[1
,12
]}

Gong, Shang Yu ^{[3
,6
]}

Tauzin, Alexandra ^{[3
,4
]}

Gasser, Romain ^{[3
,4
]}

Vezina, Dani ^{[3
,4
]}

Anand, Sai Priya ^{[3
,6
]}

Goyette, Guillaume ^{[3
]}

Chaterjee, Debashree ^{[3
]}

Ding, Shilei ^{[3
]}

Tolbert, William D. ^{[2
]}

Grunst, Michael W. ^{[1
]}

Bo, Yuxia ^{[7
,8
]}

Zhang, Shijian ^{[9
,10
]}

Richard, Jonathan ^{[3
,4
]}

Zhou, Fei ^{[11
]}

Huang, Rick K. ^{[11
]}

Esser, Lothar ^{[11
]}

Zeher, Allison ^{[11
]}

Cote, Marceline ^{[7
,8
]}

Kumar, Priti ^{[5
]}

Sodroski, Joseph ^{[9
,10
]}

Xia, Di ^{[11
]}

Uchil, Pradeep D. ^{[1
]}

Pazgier, Marzena ^{[2
]}

Finzi, Andres ^{[3
,4
,6
]}

Mothes, Walther ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Microbial Pathogenesis, 333 Cedar St, New Haven, CT 06520 USA

[2] Uniformed Serv Univ Hlth Sci, Dept Med, Div Infect Dis, Room A3060, Bethesda, MD 20814 USA

[3] Ctr Rech CHUM CRCHUM, Montreal, PQ H2X 0A9, Canada

[4] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H2X 0A9, Canada

[5] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, 333 Cedar St, New Haven, CT 06520 USA

[6] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada

[7] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada

[8] Univ Ottawa, Ctr Infect Immun & Inflammat, Ottawa, ON K1H 8M5, Canada

[9] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA

[10] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA

[11] NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA

[12] Univ Texas Hlth Sci Ctr Tyler, Dept Cellular & Mol Biol, Tyler, TX 75708 USA

来源：

CELL REPORTS | 2022年 / 38卷 / 02期

基金：

加拿大健康研究院; 美国国家卫生研究院; 加拿大创新基金会;

关键词：

RECEPTOR-BINDING DOMAIN; CRYO-EM STRUCTURE; CONFORMATIONAL DYNAMICS; CELL ENTRY; SPIKE; CORONAVIRUS; MUTATIONS; ACE2; RECONSTRUCTION; VISUALIZATION;

D O I：

10.1016/j.celrep.2021.110210

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here, we elucidate the structural basis and mode of action for two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 and CV325, which remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up"position and triggers potent shedding of the S1 subunit. In contrast, CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among beta-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in the RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.

引用

页数：28

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