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Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice

Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochlo...

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Autores principales: Zhang, Rui, Feng, Cui, Luo, Dandan, Zhao, Ruibo, Kannan, Perumal Ramesh, Yin, Yuebang, Iqbal, Muhammad Zubair, Hu, Yeting, Kong, Xiangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536476/
https://www.ncbi.nlm.nih.gov/pubmed/37765086
http://dx.doi.org/10.3390/ph16091279
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author Zhang, Rui
Feng, Cui
Luo, Dandan
Zhao, Ruibo
Kannan, Perumal Ramesh
Yin, Yuebang
Iqbal, Muhammad Zubair
Hu, Yeting
Kong, Xiangdong
author_facet Zhang, Rui
Feng, Cui
Luo, Dandan
Zhao, Ruibo
Kannan, Perumal Ramesh
Yin, Yuebang
Iqbal, Muhammad Zubair
Hu, Yeting
Kong, Xiangdong
author_sort Zhang, Rui
collection PubMed
description Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research.
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spelling pubmed-105364762023-09-29 Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice Zhang, Rui Feng, Cui Luo, Dandan Zhao, Ruibo Kannan, Perumal Ramesh Yin, Yuebang Iqbal, Muhammad Zubair Hu, Yeting Kong, Xiangdong Pharmaceuticals (Basel) Article Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research. MDPI 2023-09-11 /pmc/articles/PMC10536476/ /pubmed/37765086 http://dx.doi.org/10.3390/ph16091279 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Rui
Feng, Cui
Luo, Dandan
Zhao, Ruibo
Kannan, Perumal Ramesh
Yin, Yuebang
Iqbal, Muhammad Zubair
Hu, Yeting
Kong, Xiangdong
Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
title Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
title_full Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
title_fullStr Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
title_full_unstemmed Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
title_short Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
title_sort metformin hydrochloride significantly inhibits rotavirus infection in caco2 cell line, intestinal organoids, and mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536476/
https://www.ncbi.nlm.nih.gov/pubmed/37765086
http://dx.doi.org/10.3390/ph16091279
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