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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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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 |
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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 |
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