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-Structure paper
タイトル | Structure of the Inmazeb cocktail and resistance to Ebola virus escape. |
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ジャーナル・号・ページ | Cell Host Microbe, Vol. 31, Issue 2, Page 260-272.e7, Year 2023 |
掲載日 | 2023年2月8日 |
著者 | Vamseedhar Rayaprolu / Benjamin O Fulton / Ashique Rafique / Emilia Arturo / Dewight Williams / Chitra Hariharan / Heather Callaway / Amar Parvate / Sharon L Schendel / Diptiben Parekh / Sean Hui / Kelly Shaffer / Kristen E Pascal / Elzbieta Wloga / Stephanie Giordano / Nicole Negron / Min Ni / Richard Copin / Gurinder S Atwal / Matthew Franklin / Ruth Mabel Boytz / Callie Donahue / Robert Davey / Alina Baum / Christos A Kyratsous / Erica Ollmann Saphire / |
PubMed 要旨 | Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response ...Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.1 Å of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with the antibodies in the Inmazeb cocktail. This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach. |
リンク | Cell Host Microbe / PubMed:36708708 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 Å |
構造データ | EMDB-26005, PDB-7tn9: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / Ebola / antiviral / therapeutics / IMMUNE SYSTEM-VIRAL PROTEIN complex |