title: Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture.
abstract: Hepatitis C virus (HCV) infection is a major biomedical problem worldwide. Although new direct antiviral agents (DAAs) have been developed for the treatment of chronic HCV infection, the potential emergence of resistant virus variants and the difficulties to implement their administration worldwide make the development of novel antiviral agents an urgent need. Moreover, no effective vaccine is available against HCV and transmission of the virus still occurs particularly when prophylactic measures are not taken. We used a cell-based system to screen a battery of polyanionic carbosilane dendrimers (PCDs) to identify compounds with antiviral activity against HCV and show that they inhibit effective virus adsorption of major HCV genotypes. Interestingly, one of the PCDs irreversibly destabilized infectious virions. This compound displays additive effect in combination with a clinically relevant DAA, sofosbuvir. Our results support further characterization of these molecules as nanotools for the control of hepatitis C virus spread.
authors: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: Daniel
authors: D
authors: Sepúlveda-Crespo
authors: Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain.
authors: José Luis
authors: JL
authors: Jiménez
authors: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain.
authors: Rafael
authors: R
authors: Gómez
authors: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain.
authors: Francisco Javier
authors: FJ
authors: De La Mata
authors: Molecular Biology Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors: Pedro L
authors: PL
authors: Majano
authors: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain.
authors: Ma Ángeles
authors: MÁ
authors: Muñoz-Fernández
authors: Centro Nacional De Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus Cantoblanco, Madrid, Spain. Electronic address: pgastaminza@cnb.csic.es.
authors: Pablo
authors: P
authors: Gastaminza
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D050091:Dendrimers / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology; D012821:Silanes / Q000494:pharmacology*; D014771:Virion / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D050091:Dendrimers; D000071228:Polyelectrolytes; D011108:Polymers; D012821:Silanes; C504072:carbosilane
keywords: Antiviral; Carbosilane dendrimer; Hepatitis C virus; Nanotechnology; Virucidal