Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture

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.

Graphical AbstractPolyanionic carbosilane dendrimers (PCDs) prevent hepatitis C virus infection. Using an unbiased, cell-based screening method, different PCDs were identified as non-toxic, active compounds with antiviral activity against hepatitis C virus. The most potent compound (EC50 <5 nM; selectivity index >60,000) displays, at low doses, non-virolytic antiviral activity against the most prevalent HCV genotypes by preventing virion adsorption. Higher doses of this dendrimer (2.5 μM) are virucidal, causing destabilization of virions from different genotypes and degradation of the viral genome.94