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A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities

Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein,...

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Autores principales: Lin, Dongguo, Li, Fangfang, Wu, Qiuyi, Xie, Xiangkun, Wu, Wenjiao, Wu, Jie, Chen, Qing, Liu, Shuwen, He, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782136/
https://www.ncbi.nlm.nih.gov/pubmed/26952867
http://dx.doi.org/10.1038/srep22790
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author Lin, Dongguo
Li, Fangfang
Wu, Qiuyi
Xie, Xiangkun
Wu, Wenjiao
Wu, Jie
Chen, Qing
Liu, Shuwen
He, Jian
author_facet Lin, Dongguo
Li, Fangfang
Wu, Qiuyi
Xie, Xiangkun
Wu, Wenjiao
Wu, Jie
Chen, Qing
Liu, Shuwen
He, Jian
author_sort Lin, Dongguo
collection PubMed
description Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC(50) value of 0.53 μM against A/Puerto Rico/8/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated.
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spelling pubmed-47821362016-03-10 A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities Lin, Dongguo Li, Fangfang Wu, Qiuyi Xie, Xiangkun Wu, Wenjiao Wu, Jie Chen, Qing Liu, Shuwen He, Jian Sci Rep Article Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC(50) value of 0.53 μM against A/Puerto Rico/8/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated. Nature Publishing Group 2016-03-08 /pmc/articles/PMC4782136/ /pubmed/26952867 http://dx.doi.org/10.1038/srep22790 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lin, Dongguo
Li, Fangfang
Wu, Qiuyi
Xie, Xiangkun
Wu, Wenjiao
Wu, Jie
Chen, Qing
Liu, Shuwen
He, Jian
A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities
title A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities
title_full A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities
title_fullStr A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities
title_full_unstemmed A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities
title_short A “building block” approach to the new influenza A virus entry inhibitors with reduced cellular toxicities
title_sort “building block” approach to the new influenza a virus entry inhibitors with reduced cellular toxicities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782136/
https://www.ncbi.nlm.nih.gov/pubmed/26952867
http://dx.doi.org/10.1038/srep22790
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