Hepatitis C Virus Resistance to Carbohydrate-Binding Agents

Izquierdo, Laure; Oliveira, Catarina; Fournier, Carole; Descamps, Véronique; Morel, Virginie; Dubuisson, Jean; Brochot, Etienne; Francois, Catherine; Castelain, Sandrine; Duverlie, Gilles; Helle, Francois

With the recent approval of several direct-acting antivirals inhibiting HCV NS3/4A, NS5A or NS5B proteins, CBAs and more generally viral entry inhibitors are unlikely to find an indication for HCV treatment [50] . At best, it may be used for the prevention of graft reinfection in HCV-infected liver transplant patients or possibly for the treatment of HCV-HIV coinfected patients where drug interactions with antiretrovirals are frequently observed. However, an important feature of CBA-based therapeutic strategy is the broad antiviral spectrum. In particular, CBAs have been shown to efficiently inhibit several emergent viruses such as Dengue Virus [51] , Ebola Virus [52, 53] or Severe Acute Respiratory Syndrome Coronavirus [54, 55] . To our knowledge, viral resistance to CBAs had only been evaluated using HIV strains, which are characterized by an evolving glycan shield. Thus, our results bring new insights into the development of CBA-based antiviral strategy since they suggest that HCV resistance to CBAs is not directly conferred by mutations in the E1E2 envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms.