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Article: Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein

TitlePotent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein
Authors
Issue Date2014
Citation
Science Translational Medicine, 2014, v. 6 n. 234, p. 234ra59 How to Cite?
AbstractThe recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.
Persistent Identifierhttp://hdl.handle.net/10722/199186

 

DC FieldValueLanguage
dc.contributor.authorJiang, Len_US
dc.contributor.authorWang, Nen_US
dc.contributor.authorZuo, Ten_US
dc.contributor.authorShi, Xen_US
dc.contributor.authorPoon, KMen_US
dc.contributor.authorWu, Yen_US
dc.contributor.authorGao, Fen_US
dc.contributor.authorLi, Den_US
dc.contributor.authorWang, Ren_US
dc.contributor.authorGuo, Jen_US
dc.contributor.authorFu, Len_US
dc.contributor.authorYuen, KYen_US
dc.contributor.authorZheng, Ben_US
dc.contributor.authorWang, Xen_US
dc.contributor.authorZhang, Len_US
dc.date.accessioned2014-07-22T01:06:18Z-
dc.date.available2014-07-22T01:06:18Z-
dc.date.issued2014en_US
dc.identifier.citationScience Translational Medicine, 2014, v. 6 n. 234, p. 234ra59en_US
dc.identifier.urihttp://hdl.handle.net/10722/199186-
dc.description.abstractThe recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.en_US
dc.languageengen_US
dc.relation.ispartofScience Translational Medicineen_US
dc.titlePotent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoproteinen_US
dc.typeArticleen_US
dc.identifier.emailPoon, KM: vinpoon@hku.hken_US
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_US
dc.identifier.emailZheng, B: bzheng@hkucc.hku.hken_US
dc.identifier.authorityYuen, KY=rp00366en_US
dc.identifier.authorityZheng, B=rp00353en_US
dc.identifier.doi10.1126/scitranslmed.3008140en_US
dc.identifier.hkuros230926en_US
dc.identifier.volume6en_US
dc.identifier.issue234en_US
dc.identifier.spage234ra59en_US
dc.identifier.epage234ra59en_US

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