Metformin inhibits Zika virus infection in trophoblast cell line

Author:

González-García Luis Didier1,Velazquez-Cervantes Manuel Adrian1,Cruz-Holguin Victor Javier1,Flores-Pliego Arturo1,Carrizosa Oscar Villavicensio1,Lara-Hernandez Ignacio2,Comas-García Mauricio2,Helguera-Reppeto Addy Cecilia1,López-Ortega Orestes3,Arevalo-Romero Haruki3,Vazquez-Martinez Edgar Ricardo4,Juarez Moises Leon1

Affiliation:

1. Instituto Nacional de Perinatología

2. Universidad Autónoma de San Luis Potosí

3. Institut National de la Santé et de la Recherche Médicale (INSERM) U1151, Université Paris Descartes, Sorbonne Paris Cité

4. Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología- Universidad Nacional Autónoma de México

Abstract

Abstract Zika virus (ZIKV) infections have been associated with severe clinical outcomes, including neurological manifestations, especially in newborns with intrauterine infection. However, no licensed vaccines or specific antiviral agents are available yet. Therefore, safe and low-cost therapy is required, especially for pregnant women. In this sense, metformin, an FDA-approved drug used to treat gestational diabetes, has previously exhibited an effect anti-ZIKA in vitro in HUVEC cells by activating AMPK. In this study, we evaluated metformin treatment during in vitro ZIKV infection in a permissive trophoblast cell line JEG3. Our results demonstrate that metformin impacts viral replication and protein synthesis and reverts the cytoskeletal changes promoted by ZIKV infection. Beyond this, lipid droplet formation is reduced, which is associated with the lipogenic activation of infection. Taken together, our findings indicate that metformin has potential as an antiviral agent against in vitro ZIKV infection in trophoblastic cells.

Publisher

Research Square Platform LLC

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