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-Structure paper
タイトル | Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody. |
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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 | EMDB-24876, PDB-7s6i: EMDB-24877, PDB-7s6j: EMDB-24878, PDB-7s6k: EMDB-24879, PDB-7s6l: EMDB-26389: J08 fragment antigen binding in complex with Omicron SARS-CoV-2-6P S protein PDB-7sbu: |
化合物 | ChemComp-NAG: ChemComp-GOL: ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN/Immune System (ウイルス性) / COVID (新型コロナウイルス感染症 (2019年)) / SARS (重症急性呼吸器症候群) / CoV-2 / viral glycoprotein / Spike / stabilizing mutations / coronavirus (オルトコロナウイルス亜科) / VIRAL PROTEIN (ウイルスタンパク質) / VIRAL PROTEIN-Immune System complex (ウイルス性) / ultrapotent antibody / neutralizing antibody (中和抗体) / IMMUNE SYSTEM (免疫系) / SARS-CoV-2 (SARSコロナウイルス2) / Antibody (抗体) / COVID-19 (新型コロナウイルス感染症 (2019年)) / receptor binding domain (受容体) |