The antiviral effect of metformin on zika and dengue virus infection

Abstract The Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FD...

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Autores principales:	Carlos Noe Farfan-Morales, Carlos Daniel Cordero-Rivera, Juan Fidel Osuna-Ramos, Irma Eloisa Monroy-Muñoz, Luis Adrián De Jesús-González, José Esteban Muñoz-Medina, Arianna M. Hurtado-Monzón, José Manuel Reyes-Ruiz, Rosa María del Ángel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99b3d1903c434287a00a93a62d4dfce1
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spelling	oai:doaj.org-article:99b3d1903c434287a00a93a62d4dfce12021-12-02T17:32:56ZThe antiviral effect of metformin on zika and dengue virus infection10.1038/s41598-021-87707-92045-2322https://doaj.org/article/99b3d1903c434287a00a93a62d4dfce12021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87707-9https://doaj.org/toc/2045-2322Abstract The Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity. In this study, MET treatment was evaluated during in vitro and in vivo ZIKV infection and compared to MET treatment during DENV infection. Our results demonstrated that MET has a broad in vitro antiviral spectrum. MET inhibited ZIKV infection in different cell lines, but it was most effective in inhibiting DENV and yellow fever virus (YFV) infection in Huh-7 cells. However, the drug failed to protect against ZIKV infection when AG129 immunodeficient mice were used as in vivo model. Interestingly, MET increased DENV-infected male mice's survival time, reducing the severe signs of the disease. Together, these findings indicate that, although MET was an effective antiviral agent to inhibit in vitro and in vivo DENV infection, it could only inhibit in vitro ZIKV infection.Carlos Noe Farfan-MoralesCarlos Daniel Cordero-RiveraJuan Fidel Osuna-RamosIrma Eloisa Monroy-MuñozLuis Adrián De Jesús-GonzálezJosé Esteban Muñoz-MedinaArianna M. Hurtado-MonzónJosé Manuel Reyes-RuizRosa María del ÁngelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carlos Noe Farfan-Morales Carlos Daniel Cordero-Rivera Juan Fidel Osuna-Ramos Irma Eloisa Monroy-Muñoz Luis Adrián De Jesús-González José Esteban Muñoz-Medina Arianna M. Hurtado-Monzón José Manuel Reyes-Ruiz Rosa María del Ángel The antiviral effect of metformin on zika and dengue virus infection
description	Abstract The Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity. In this study, MET treatment was evaluated during in vitro and in vivo ZIKV infection and compared to MET treatment during DENV infection. Our results demonstrated that MET has a broad in vitro antiviral spectrum. MET inhibited ZIKV infection in different cell lines, but it was most effective in inhibiting DENV and yellow fever virus (YFV) infection in Huh-7 cells. However, the drug failed to protect against ZIKV infection when AG129 immunodeficient mice were used as in vivo model. Interestingly, MET increased DENV-infected male mice's survival time, reducing the severe signs of the disease. Together, these findings indicate that, although MET was an effective antiviral agent to inhibit in vitro and in vivo DENV infection, it could only inhibit in vitro ZIKV infection.
format	article
author	Carlos Noe Farfan-Morales Carlos Daniel Cordero-Rivera Juan Fidel Osuna-Ramos Irma Eloisa Monroy-Muñoz Luis Adrián De Jesús-González José Esteban Muñoz-Medina Arianna M. Hurtado-Monzón José Manuel Reyes-Ruiz Rosa María del Ángel
author_facet	Carlos Noe Farfan-Morales Carlos Daniel Cordero-Rivera Juan Fidel Osuna-Ramos Irma Eloisa Monroy-Muñoz Luis Adrián De Jesús-González José Esteban Muñoz-Medina Arianna M. Hurtado-Monzón José Manuel Reyes-Ruiz Rosa María del Ángel
author_sort	Carlos Noe Farfan-Morales
title	The antiviral effect of metformin on zika and dengue virus infection
title_short	The antiviral effect of metformin on zika and dengue virus infection
title_full	The antiviral effect of metformin on zika and dengue virus infection
title_fullStr	The antiviral effect of metformin on zika and dengue virus infection
title_full_unstemmed	The antiviral effect of metformin on zika and dengue virus infection
title_sort	antiviral effect of metformin on zika and dengue virus infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/99b3d1903c434287a00a93a62d4dfce1
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The antiviral effect of metformin on zika and dengue virus infection

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