Antiviral Effect of Triple Combination of VP1 Ligands against Coxsackievirus B3 Infection in Newborn Mice

Abstract

The Coxsackie B viruses (CVB), are distributed worldwide and cause a broad spectrum of diseases. Currently, clinically effective antivirals for the treatment of these infections do not exist. It was found that the unsatisfactory effectiveness of enteroviral inhibitors in vivo has been associated with the rapid development of drug resistance and that explains why effective antivirals have failed in monotherapy trials. Combination therapy with two or more drugs has the potential to successfully inhibit viral infection more effectively than either drug alone. It could achieve greater effects and avoid side effects using lower drug concentrations, and thus, they could prevent the rapid development of drug resistance. In this work, we examine the combined treatment effect of three enterovirus replication inhibitors – pleconaril, pocapavir, and vapendavir, which are VP1 hydrophobic pocket ligands. All of them have passed clinical double-blind trials as monotherapy courses, but none of them have been approved for clinical application, because of slide effects. We evaluate the effectiveness of the combination pleconaril/pocapavir/vapendavir (PPV) applied via CAA treatment scheme on Coxsackievirus B3 (CVB3) infection in newborn mice.