中国军事医学科学院秦川等研究人员合作揭示高效SARS-CoV-2抗体的结构基础。该研究于2020年9月14日在线发表于《细胞》。

Title: Structurally resolved SARS-CoV-2 antibody shows high efficacy in severely infected hamsters and provides a potent cocktail pairing strategy

Author: Shuo Du, Yunlong Cao, Qinyu Zhu, Pin Yu, Feifei Qi, Guopeng Wang, Xiaoxia Du, Linlin Bao, Wei Deng, Hua 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, X. Sunney Xie, Xiao-dong Su, Junyu Xiao, Chuan Qin

Issue&Volume: 2020-09-14

Abstract: 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- 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 RBD. 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.

DOI: 10.1016/j.cell.2020.09.035

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31232-0