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TitleFunctional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 2904, Year 2021
Publish dateMay 18, 2021
AuthorsChao Zhang / Cong Xu / Wenlong Dai / Yifan Wang / Zhi Liu / Xueyang Zhang / Xuesong Wang / Haikun Wang / Sitang Gong / Yao Cong / Zhong Huang /
PubMed AbstractEnterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), ...Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.
External linksNat Commun / PubMed:34006855 / PubMed Central
MethodsEM (single particle)
Resolution2.89 - 3.6 Å
Structure data

31054

7ebr

EMDB-31054, PDB-7ebr:
EV-D68 in complex with 2H12 Fab (state S2)
Method: EM (single particle) / Resolution: 3.6 Å

31055

7ebz

EMDB-31055, PDB-7ebz:
EV-D68 in complex with 2H12 Fab (state S1)
Method: EM (single particle) / Resolution: 3.09 Å

31056

7ec5

EMDB-31056, PDB-7ec5:
EV-D68 in complex with 8F12 Fab
Method: EM (single particle) / Resolution: 2.89 Å

31060

7ecy

EMDB-31060, PDB-7ecy:
EV-D68 in complex with 2H12 Fab (State 3)
Method: EM (single particle) / Resolution: 3.6 Å

Source
  • mus musculus (house mouse)
  • EV68, EV-68
  • mouse (mice)
  • mouse
  • Enterovirus D68
  • human enterovirus d68
KeywordsVIRUS / Enterovirus D68 / Monoclonal antibody / Uncoating / Monoclonal antibody; Uncoating

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