Cholesterol-Lowering Drugs as Potential Antivirals: A Repurposing Approach against Flavivirus Infections
Juan Fidel Osuna-Ramos,
Carlos Noe Farfan-Morales,
Carlos Daniel Cordero-Rivera,
Luis Adrián De Jesús-González,
José Manuel Reyes-Ruiz,
Arianna M. Hurtado-Monzón,
Selvin Noé Palacios-Rápalo,
Ricardo Jiménez-Camacho,
Marco Antonio Meraz-Ríos,
Rosa María Del Ángel
Affiliations
Juan Fidel Osuna-Ramos
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Carlos Noe Farfan-Morales
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Carlos Daniel Cordero-Rivera
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Luis Adrián De Jesús-González
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
José Manuel Reyes-Ruiz
Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 14, Centro Médico Nacional “Adolfo Ruiz Cortines”, Instituto Mexicano del Seguro Social (IMSS), Veracruz Norte, Veracruz 91810, Mexico
Arianna M. Hurtado-Monzón
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Selvin Noé Palacios-Rápalo
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Ricardo Jiménez-Camacho
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Marco Antonio Meraz-Ríos
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City 07360, Mexico
Rosa María Del Ángel
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico
Flaviviruses, including Dengue (DENV), Zika (ZIKV), and Yellow Fever (YFV) viruses, represent a significant global health burden. The development of effective antiviral therapies against these viruses is crucial to mitigate their impact. This study investigated the antiviral potential of the cholesterol-lowering drugs atorvastatin and ezetimibe in monotherapy and combination against DENV, ZIKV, and YFV. In vitro results demonstrated a dose-dependent reduction in the percentage of infected cells for both drugs. The combination of atorvastatin and ezetimibe showed a synergistic effect against DENV 2, an additive effect against DENV 4 and ZIKV, and an antagonistic effect against YFV. In AG129 mice infected with DENV 2, monotherapy with atorvastatin or ezetimibe significantly reduced clinical signs and increased survival. However, the combination of both drugs did not significantly affect survival. This study provides valuable insights into the potential of atorvastatin and ezetimibe as antiviral agents against flaviviruses and highlights the need for further investigations into their combined therapeutic effects.
