Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy | Zendy

Shuo Du | Zendy; Yunlong Cao | Zendy; Qinyu Zhu | Zendy; Pin Yü | Zendy; Feifei Qi | Zendy; Guopeng Wang | Zendy; Xiaoxia Du | Zendy; Linlin Bao | Zendy; Wei Deng | Zendy; Huachen Zhu | Zendy; Jiangning Liu | Zendy; Jianhui Nie | Zendy; Yinghui Zheng | Zendy; Haoyu Liang | Zendy; Ruixue Liu | Zendy; Shuran Gong | Zendy; Hua Xu | Zendy; Ayijiang Yisimayi | Zendy; Qi Lv | Zendy; Bo Wang | Zendy; Runsheng He | Zendy; Yunlin Han | Zendy; Wenjie Zhao | Zendy; Yali Bai | Zendy; Yajin Qu | Zendy; Xiang Gao | Zendy; Chenggong Ji | Zendy; Qisheng Wang | Zendy; Ning Gao | Zendy; Weijin Huang | Zendy; Youchun Wang | Zendy; Xiaoliang Sunney Xie | Zendy; XiaoDong Su | Zendy; Junyu Xiao | Zendy; Chuan Qin | Zendy

Open Access

Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy

Author(s) -

Shuo Du,

Yunlong Cao,

Qinyu Zhu,

Pin Yü,

Feifei Qi,

Guopeng Wang,

Xiaoxia Du,

Linlin Bao,

Wei Deng,

Huachen Zhu,

Jiangning Liu,

Jianhui Nie,

Yinghui Zheng,

Haoyu Liang,

Ruixue Liu,

Shuran Gong,

Hua Xu,

Ayijiang Yisimayi,

Qi Lv,

Bo Wang,

Runsheng He,

Yunlin Han,

Wenjie Zhao,

Yali Bai,

Yajin Qu,

Xiang Gao,

Chenggong Ji,

Qisheng Wang,

Ning Gao,

Weijin Huang,

Youchun Wang,

Xiaoliang Sunney Xie,

XiaoDong Su,

Junyu Xiao,

Chuan Qin

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.09.035

Subject(s) - neutralization , potency , biology , epitope , hamster , antibody , virology , neutralizing antibody , pairing , covid-19 , mesocricetus , microbiology and biotechnology , immunology , in vitro , genetics , medicine , superconductivity , physics , disease , quantum mechanics , infectious disease (medical specialty)

Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.

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