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-Structure paper
タイトル | IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 5814, Year 2022 |
掲載日 | 2022年10月3日 |
![]() | Matthew R Chang / Luke Tomasovic / Natalia A Kuzmina / Adam J Ronk / Patrick O Byrne / Rebecca Johnson / Nadia Storm / Eduardo Olmedillas / Yixuan J Hou / Alexandra Schäfer / Sarah R Leist / Longping V Tse / Hanzhong Ke / Christian Coherd / Katrina Nguyen / Maliwan Kamkaew / Anna Honko / Quan Zhu / Galit Alter / Erica Ollmann Saphire / Jason S McLellan / Anthony Griffiths / Ralph S Baric / Alexander Bukreyev / Wayne A Marasco / ![]() |
PubMed 要旨 | Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being ...Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern. |
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手法 | EM (単粒子) |
解像度 | 3.0 - 4.6 Å |
構造データ | ![]() EMDB-25618: SARS-CoV-2 VFLIP spike boung to 2 Ab12 Fab fragments EMDB-25663, PDB-7t3m: ![]() EMDB-25689: SARS-CoV-2 S (Spike Glycoprotein) D614G with Three (3) RBDs Up, Bound to Antibody 2-7 scFv, global map with poorly-resolved RBDs and scFvs ![]() EMDB-25690: SARS-CoV-2 S (Spike Glycoprotein) D614G with Three (3) RBDs Up, Bound to Antibody 2-7 scFv, local refinement map EMDB-25711, PDB-7t67: |
化合物 | ![]() ChemComp-NAG: |
由来 |
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / virus / coronavirus / SARS CoV-2 / SARS-CoV-2 / spike / 2-7 / D614G / RBD / 3 RBDs up / three RBDs up / scFv / complex / phage display / VIRAL PROTEIN / local refinement / focused refinement / VIRAL PROTEIN-IMMUNE SYSTEM complex / 1 RBD up / one RBD up |