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TitleStructure of the Inmazeb cocktail and resistance to Ebola virus escape.
Journal, issue, pagesCell Host Microbe, Vol. 31, Issue 2, Page 260-272.e7, Year 2023
Publish dateFeb 8, 2023
AuthorsVamseedhar 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 AbstractMonoclonal 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.
External linksCell Host Microbe / PubMed:36708708 / PubMed Central
MethodsEM (single particle)
Resolution3.1 Å
Structure data

26005

7tn9

EMDB-26005, PDB-7tn9:
Structure of the Inmazeb cocktail and resistance to escape against Ebola virus
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • mus musculus (house mouse)
  • Ebola virus - Mayinga, Zaire, 1976
  • ebola virus - mayinga
  • zaire, 1976
KeywordsIMMUNE SYSTEM/VIRAL PROTEIN / Ebola / antiviral / therapeutics / IMMUNE SYSTEM-VIRAL PROTEIN complex

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