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-Structure paper
タイトル | Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 3661, Year 2021 |
掲載日 | 2021年6月16日 |
著者 | Edurne Rujas / Iga Kucharska / Yong Zi Tan / Samir Benlekbir / Hong Cui / Tiantian Zhao / Gregory A Wasney / Patrick Budylowski / Furkan Guvenc / Jocelyn C Newton / Taylor Sicard / Anthony Semesi / Krithika Muthuraman / Amy Nouanesengsy / Clare Burn Aschner / Katherine Prieto / Stephanie A Bueler / Sawsan Youssef / Sindy Liao-Chan / Jacob Glanville / Natasha Christie-Holmes / Samira Mubareka / Scott D Gray-Owen / John L Rubinstein / Bebhinn Treanor / Jean-Philippe Julien / |
PubMed 要旨 | SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a ...SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC) values as low as 9 × 10 M are achieved as a result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multi-Affinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity together with multi-specificity to deliver ultrapotent and broad neutralizers against SARS-CoV-2. The modularity of the platform also makes it relevant for rapid evaluation against other infectious diseases of global health importance. Neutralizing antibodies are a promising therapeutic for SARS-CoV-2. |
リンク | Nat Commun / PubMed:34135340 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.95 - 6.2 Å |
構造データ | EMDB-22738: EMDB-22739: EMDB-22740: EMDB-22741: PDB-7k9z: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM (免疫系) / SARS-CoV-2 (SARSコロナウイルス2) / Receptor Binding Domain (受容体) / Neutralizing antibodies (中和抗体) |