Cargando…

Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway

Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral m...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Huan, Zhao, Pu, Zhang, Caisheng, Ming, Xin, Zhang, Chaofeng, Jung, Yong-Sam, Qian, Yingjuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661853/
https://www.ncbi.nlm.nih.gov/pubmed/37923169
http://dx.doi.org/10.1016/j.virusres.2023.199260
_version_ 1785138073501171712
author Chen, Huan
Zhao, Pu
Zhang, Caisheng
Ming, Xin
Zhang, Chaofeng
Jung, Yong-Sam
Qian, Yingjuan
author_facet Chen, Huan
Zhao, Pu
Zhang, Caisheng
Ming, Xin
Zhang, Chaofeng
Jung, Yong-Sam
Qian, Yingjuan
author_sort Chen, Huan
collection PubMed
description Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral mechanism of Veratramine (VAM), which actively inhibits PEDV replication with a 50 % inhibitory concentration (IC(50)) of ∼5 µM. Upon VAM treatment, both PEDV-nucleocapsid (N) protein level and virus titer decreased significantly. The time-of-addition assay results showed that VAM could inhibit PEDV replication by blocking viral entry. Importantly, VAM could inhibit PEDV-induced phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) activity and further suppress micropinocytosis, which is required for PEDV entry. In addition, PI3K inhibitor LY294002 showed anti-PEDV activity by blocking viral entry as well. Taken together, VAM possessed anti-PEDV properties against the entry stage of PEDV by inhibiting the macropinocytosis pathway by suppressing the PI3K/Akt pathway. VAM could be considered as a lead compound for the development of anti-PEDV drugs and may be used during the viral entry stage of PEDV infection.
format Online
Article
Text
id pubmed-10661853
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-106618532023-11-08 Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway Chen, Huan Zhao, Pu Zhang, Caisheng Ming, Xin Zhang, Chaofeng Jung, Yong-Sam Qian, Yingjuan Virus Res Article Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral mechanism of Veratramine (VAM), which actively inhibits PEDV replication with a 50 % inhibitory concentration (IC(50)) of ∼5 µM. Upon VAM treatment, both PEDV-nucleocapsid (N) protein level and virus titer decreased significantly. The time-of-addition assay results showed that VAM could inhibit PEDV replication by blocking viral entry. Importantly, VAM could inhibit PEDV-induced phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) activity and further suppress micropinocytosis, which is required for PEDV entry. In addition, PI3K inhibitor LY294002 showed anti-PEDV activity by blocking viral entry as well. Taken together, VAM possessed anti-PEDV properties against the entry stage of PEDV by inhibiting the macropinocytosis pathway by suppressing the PI3K/Akt pathway. VAM could be considered as a lead compound for the development of anti-PEDV drugs and may be used during the viral entry stage of PEDV infection. Elsevier 2023-11-08 /pmc/articles/PMC10661853/ /pubmed/37923169 http://dx.doi.org/10.1016/j.virusres.2023.199260 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
spellingShingle Article
Chen, Huan
Zhao, Pu
Zhang, Caisheng
Ming, Xin
Zhang, Chaofeng
Jung, Yong-Sam
Qian, Yingjuan
Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway
title Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway
title_full Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway
title_fullStr Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway
title_full_unstemmed Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway
title_short Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway
title_sort veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing pi3k/akt pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661853/
https://www.ncbi.nlm.nih.gov/pubmed/37923169
http://dx.doi.org/10.1016/j.virusres.2023.199260
work_keys_str_mv AT chenhuan veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway
AT zhaopu veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway
AT zhangcaisheng veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway
AT mingxin veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway
AT zhangchaofeng veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway
AT jungyongsam veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway
AT qianyingjuan veratramineinhibitsporcineepidemicdiarrheavirusentrythroughmacropinocytosisbysuppressingpi3kaktpathway