Cargando…
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,...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782419902370414592 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4782136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lindongguo abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT lifangfang abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT wuqiuyi abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT xiexiangkun abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT wuwenjiao abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT wujie abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT chenqing abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT liushuwen abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT hejian abuildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT lindongguo buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT lifangfang buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT wuqiuyi buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT xiexiangkun buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT wuwenjiao buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT wujie buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT chenqing buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT liushuwen buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities AT hejian buildingblockapproachtothenewinfluenzaavirusentryinhibitorswithreducedcellulartoxicities |