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-Structure paper
タイトル | Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations. |
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ジャーナル・号・ページ | J Mol Biol, Vol. 433, Issue 19, Page 167177, Year 2021 |
掲載日 | 2021年9月17日 |
著者 | Shane Miersch / Zhijie Li / Reza Saberianfar / Mart Ustav / James Brett Case / Levi Blazer / Chao Chen / Wei Ye / Alevtina Pavlenco / Maryna Gorelik / Julia Garcia Perez / Suryasree Subramania / Serena Singh / Lynda Ploder / Safder Ganaie / Rita E Chen / Daisy W Leung / Pier Paolo Pandolfi / Giuseppe Novelli / Giulia Matusali / Francesca Colavita / Maria R Capobianchi / Suresh Jain / J B Gupta / Gaya K Amarasinghe / Michael S Diamond / James Rini / Sachdev S Sidhu / |
PubMed 要旨 | Neutralizing antibodies (nAbs) hold promise as therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic ...Neutralizing antibodies (nAbs) hold promise as therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic bivalent and tetravalent nAbs against SARS-CoV-2. The best nAb targets the host receptor binding site of the viral S-protein and tetravalent versions block entry with a potency exceeding bivalent nAbs by an order of magnitude. Structural studies show that both the bivalent and tetravalent nAbs can make multivalent interactions with a single S-protein trimer, consistent with the avidity and potency of these molecules. Significantly, we show that the tetravalent nAbs show increased tolerance to potential virus escape mutants and an emerging variant of concern. Bivalent and tetravalent nAbs can be produced at large-scale and are as stable and specific as approved antibody drugs. Our results provide a general framework for enhancing antiviral therapies against COVID-19 and related viral threats, and our strategy can be applied to virtually any antibody drug. |
リンク | J Mol Biol / PubMed:34329642 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3 - 6.4 Å |
構造データ | EMDB-22925, PDB-7kmk: EMDB-22926, PDB-7kml: EMDB-23064, PDB-7kxj: EMDB-23065, PDB-7kxk: PDB-7klg: PDB-7klh: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/Immune System / SARS-CoV-2 / spike glycoprotein / Fab / VIRAL PROTEIN-Immune System complex / spike / VIRAL PROTEIN |