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-Structure paper
タイトル | Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants. |
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ジャーナル・号・ページ | bioRxiv, Year 2021 |
掲載日 | 2021年3月1日 |
著者 | Lingshu Wang / Tongqing Zhou / Yi Zhang / Eun Sung Yang / Chaim A Schramm / Wei Shi / Amarendra Pegu / Olamide K Oloninyi / Amy Ransier / Samuel Darko / Sandeep R Narpala / Christian Hatcher / David R Martinez / Yaroslav Tsybovsky / Emily Phung / Olubukola M Abiona / Evan M Cale / Lauren A Chang / Kizzmekia S Corbett / Anthony T DiPiazza / Ingelise J Gordon / Kwanyee Leung / Tracy Liu / Rosemarie D Mason / Alexandra Nazzari / Laura Novik / Adam S Olia / Nicole A Doria-Rose / Tyler Stephens / Christopher D Stringham / Chloe Adrienna Talana / I-Ting Teng / Danielle Wagner / Alicia T Widge / Baoshan Zhang / Mario Roederer / Julie E Ledgerwood / Tracy J Ruckwardt / Martin R Gaudinski / Ralph S Baric / Barney S Graham / Adrian B McDermott / Daniel C Douek / Peter D Kwong / John R Mascola / Nancy J Sullivan / John Misasi / |
PubMed 要旨 | The emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We ...The emergence of highly transmissible SARS-CoV-2 variants of concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identify four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 12 variants including the B.1.1.7 and B.1.351 VOCs. Two of them are ultrapotent, with sub-nanomolar neutralization titers (IC50 <0.0006 to 0.0102 μ g/mL; IC80 < 0.0006 to 0.0251 μ g/mL). We define the structural and functional determinants of binding for all four VOC-targeting antibodies, and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting potential means to mitigate resistance development. These results define the basis of therapeutic cocktails against VOCs and suggest that targeted boosting of existing immunity may increase vaccine breadth against VOCs. |
リンク | bioRxiv / PubMed:33655252 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.29 Å |
構造データ | EMDB-25792, PDB-7tb4: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / SARS-CoV-2 / spike / Omicron / variant of concern |