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Structure paper

タイトル	Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 119, Issue 20, Page e2120976119, Year 2022
掲載日	2022年5月17日
著者	Jonathan L Torres / Gabriel Ozorowski / Emanuele Andreano / Hejun Liu / Jeffrey Copps / Giulia Piccini / Lorena Donnici / Matteo Conti / Cyril Planchais / Delphine Planas / Noemi Manganaro / Elisa Pantano / Ida Paciello / Piero Pileri / Timothée Bruel / Emanuele Montomoli / Hugo Mouquet / Olivier Schwartz / Claudia Sala / Raffaele De Francesco / Ian A Wilson / Rino Rappuoli / Andrew B Ward /
PubMed 要旨	As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome ...As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryoelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.
リンク	Proc Natl Acad Sci U S A / PubMed:35549549 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.53 - 6.0 Å
構造データ	24876 7s6i EMDB-24876, PDB-7s6i: SARS-CoV-2-6P-Mut2 S protein 手法: EM (単粒子) / 解像度: 3.2 Å 24877 7s6j EMDB-24877, PDB-7s6j: J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut2 S protein (conformation 1) 手法: EM (単粒子) / 解像度: 3.4 Å 24878 7s6k EMDB-24878, PDB-7s6k: J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut2 S protein (conformation 2) 手法: EM (単粒子) / 解像度: 3.4 Å 24879 7s6l EMDB-24879, PDB-7s6l: J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (conformation 3) 手法: EM (単粒子) / 解像度: 4.0 Å EMDB-26389: J08 fragment antigen binding in complex with Omicron SARS-CoV-2-6P S protein 手法: EM (単粒子) / 解像度: 6.0 Å PDB-7sbu: Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a highly potent antibody J08 Fab 手法: X-RAY DIFFRACTION / 解像度: 2.53 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-GOL: GLYCEROL / グリセロ-ル ChemComp-HOH: WATER
由来	severe acute respiratory syndrome coronavirus 2 (ウイルス) homo sapiens (ヒト)
キーワード	VIRAL PROTEIN/Immune System / COVID / SARS / CoV-2 / viral glycoprotein / Spike / stabilizing mutations / coronavirus / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / ultrapotent antibody / neutralizing antibody / IMMUNE SYSTEM / SARS-CoV-2 / Antibody / COVID-19 / receptor binding domain