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Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication

BACKGROUND: Enterovirus A 71 (EV71) is a neurotropic virus that may lead to acute flaccid paralysis, encephalitis, cardiopulmonary failure or even death. No vaccine and defensive drug controlling EV71 is currently available, novel and efficient antiviral drug or vaccine is therefore urgently needed....

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Detalles Bibliográficos
Autores principales: Li, Yaoming, Yu, Jie, Qi, Xiuwen, Yan, Huimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343263/
https://www.ncbi.nlm.nih.gov/pubmed/30669993
http://dx.doi.org/10.1186/s12865-019-0288-x
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author Li, Yaoming
Yu, Jie
Qi, Xiuwen
Yan, Huimin
author_facet Li, Yaoming
Yu, Jie
Qi, Xiuwen
Yan, Huimin
author_sort Li, Yaoming
collection PubMed
description BACKGROUND: Enterovirus A 71 (EV71) is a neurotropic virus that may lead to acute flaccid paralysis, encephalitis, cardiopulmonary failure or even death. No vaccine and defensive drug controlling EV71 is currently available, novel and efficient antiviral drug or vaccine is therefore urgently needed. 3D(pol) (RNA-dependent RNA polymerase (RdRp)) has been an important target for anti-EV71 drug development. METHODS: A panel of monoclonal IgG antibodies (mAbs) against EV71 3D(pol) were generated by traditional cell fusion methods. And the antibody affinity and specificity to EV71 3D(pol) were evaluated by Enzyme-linked Immunosorbent Assay (ELISA), Indirect Fluorescent Assay (IFA) and Western blotting. Antiviral activities of these antibodies were also determined in vitro and in vivo. RESULTS: Two mAbs towards EV71 3D(pol) were able to effectively suppress EV71 replication in Vero-1008 cell when intracellarly delivered. And they also dampened the RNA polymerase activity of 3D(pol) in vitro. More importantly, these mAbs provided partial protection in EV71-challenged neonatal murine challenge model. CONCLUSIONS: These results showed that two of mAbs against EV71 3D(pol) inhibited EV71 replication and could be utilized as promising therapeutic drug candidate. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12865-019-0288-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-63432632019-01-24 Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication Li, Yaoming Yu, Jie Qi, Xiuwen Yan, Huimin BMC Immunol Research Article BACKGROUND: Enterovirus A 71 (EV71) is a neurotropic virus that may lead to acute flaccid paralysis, encephalitis, cardiopulmonary failure or even death. No vaccine and defensive drug controlling EV71 is currently available, novel and efficient antiviral drug or vaccine is therefore urgently needed. 3D(pol) (RNA-dependent RNA polymerase (RdRp)) has been an important target for anti-EV71 drug development. METHODS: A panel of monoclonal IgG antibodies (mAbs) against EV71 3D(pol) were generated by traditional cell fusion methods. And the antibody affinity and specificity to EV71 3D(pol) were evaluated by Enzyme-linked Immunosorbent Assay (ELISA), Indirect Fluorescent Assay (IFA) and Western blotting. Antiviral activities of these antibodies were also determined in vitro and in vivo. RESULTS: Two mAbs towards EV71 3D(pol) were able to effectively suppress EV71 replication in Vero-1008 cell when intracellarly delivered. And they also dampened the RNA polymerase activity of 3D(pol) in vitro. More importantly, these mAbs provided partial protection in EV71-challenged neonatal murine challenge model. CONCLUSIONS: These results showed that two of mAbs against EV71 3D(pol) inhibited EV71 replication and could be utilized as promising therapeutic drug candidate. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12865-019-0288-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-22 /pmc/articles/PMC6343263/ /pubmed/30669993 http://dx.doi.org/10.1186/s12865-019-0288-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Li, Yaoming
Yu, Jie
Qi, Xiuwen
Yan, Huimin
Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication
title Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication
title_full Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication
title_fullStr Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication
title_full_unstemmed Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication
title_short Monoclonal antibody against EV71 3D(pol) inhibits the polymerase activity of RdRp and virus replication
title_sort monoclonal antibody against ev71 3d(pol) inhibits the polymerase activity of rdrp and virus replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343263/
https://www.ncbi.nlm.nih.gov/pubmed/30669993
http://dx.doi.org/10.1186/s12865-019-0288-x
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