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Structure paper

タイトル	Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern.
ジャーナル・号・ページ	Cell Rep, Vol. 38, Issue 2, Page 110210, Year 2022
掲載日	2022年1月11日
著者	Wenwei Li / Yaozong Chen / Jérémie Prévost / Irfan Ullah / Maolin Lu / Shang Yu Gong / Alexandra Tauzin / Romain Gasser / Dani Vézina / Sai Priya Anand / Guillaume Goyette / Debashree Chaterjee / Shilei Ding / William D Tolbert / Michael W Grunst / Yuxia Bo / Shijian Zhang / Jonathan Richard / Fei Zhou / Rick K Huang / Lothar Esser / Allison Zeher / Marceline Côté / Priti Kumar / Joseph Sodroski / Di Xia / Pradeep D Uchil / Marzena Pazgier / Andrés Finzi / Walther Mothes /
PubMed 要旨	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 ...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 CV3-25, 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 β-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.
リンク	Cell Rep / PubMed:34971573 / PubMed Central
手法	EM (単粒子) / EM (サブトモグラム平均) / X線回折
解像度	2.15 - 12.0 Å
構造データ	EMDB-25200: CryoEM structure of SARS-CoV-2 HexaPro spike in complex with S2-binding CV3-25 手法: EM (単粒子) / 解像度: 3.49 Å EMDB-25564: Subtomogram averaging of SARS-CoV-2 Spike Protein bound to CV3-1 手法: EM (サブトモグラム平均) / 解像度: 12.0 Å EMDB-25565: Subtomogram averaging of SARS-CoV-2 Spike Protein bound to Fab CV3-25 手法: EM (サブトモグラム平均) / 解像度: 10.0 Å EMDB-25566: Subtomogram averaging of SARS-CoV-2 Spike Protein 手法: EM (サブトモグラム平均) / 解像度: 10.0 Å PDB-7nab: Crystal structure of human neutralizing mAb CV3-25 binding to SARS-CoV-2 S MPER peptide 1140-1165 手法: X-RAY DIFFRACTION / 解像度: 2.15 Å
化合物	ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-CIT: CITRIC ACID / クエン酸 / クエン酸 ChemComp-HOH: WATER / 水
由来	homo sapiens (ヒト) severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2)
キーワード	VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / human neutralizing mAb / MPER-targeting / SARS-CoV-2 (SARSコロナウイルス2) / spike / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性)