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TitleProtection against lethal canine distemper virus infection by a dual epitope-targeting synthetic antibody.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 103, Year 2026
Publish dateJan 7, 2026
AuthorsMelanie Scherer / Nadia Djabeur / Oliver Siering / Jean-Marc Jeckelmann / Marianne Wyss / Marina Cresci / Morgane Di Palma Subran / Rainer Riedl / Patrick Chames / Christian K Pfaller / Bevan Sawatsky / Dimitrios Fotiadis / Philippe Plattet /
PubMed AbstractDespite vaccine availability, the morbilliviruses measles virus and canine distemper virus (CDV) are still causing major health impairments in human and animal populations. Here, we identified two ...Despite vaccine availability, the morbilliviruses measles virus and canine distemper virus (CDV) are still causing major health impairments in human and animal populations. Here, we identified two potent, neutralizing single domain antibodies directed against the tetrameric receptor binding (H) protein of CDV. Structural analyses spotlighted two vulnerable sites within the H protein. While the first overlaps with the receptor binding site, the second encompasses amino acid residues of two protomers located at the distal dimeric head interface, which supports distinct mechanisms of neutralization. Upon application of an engineered tetravalent and biparatopic antibody, ferrets were protected at a remarkably low antibody dose (1 mg/kg) administered intra-peritoneally on days 3 and 7 post-exposure of a lethal CDV challenge. Collectively, this study spotlights the power of integrating multiple mechanisms of neutralization in a single format and provides a roadmap to design next-generation therapeutics against morbilliviral infections as well as other infectious pathogens.
External linksNat Commun / PubMed:41501035 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.3 Å
Structure data

EMDB-52020: Cryo-EM consensus map of the canine distemper virus tetrameric attachment H glycoprotein in complex with two different Nanobodies
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-52021: Cryo-EM focused refined map of the canine distemper virus dimer II region of the tetrameric attachment H glycoprotein in complex with two different Nanobodies
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-52023: Cryo-EM focused refined map of the canine distemper virus dimer I region of the tetrameric attachment H glycoprotein in complex with two different Nanobodies
Method: EM (single particle) / Resolution: 3.1 Å

52024

9hbp

EMDB-52024, PDB-9hbp:
Cryo-EM structure of the canine distemper virus tetrameric attachment H glycoprotein in complex with two different Nanobodies
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • morbillivirus canis
  • lama glama (llama)
KeywordsVIRAL PROTEIN / canine distemper virus / hemagglutinine / CDV / H-protein / Complex / Nanobody

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