Respiratory syncytial virus (RSV) and influenza virus are the principal contributors to respiratory tract infections worldwide. Clinical treatment of RSV or influenza A virus (IAV) is limited and may be postponed because of misdiagnosis or coinfection with multiple pathogens. Here, we described VV251, the prodrug of 4'-fluorouridine, a novel oral nucleoside analog that exhibits potent inhibitory activity against RSV laboratory strains and clinical isolates, as well as IAV, in vitro. The EC50 values of VV251 against these viruses ranged from nanomolar to low micromolar. Moreover, VV251 significantly reduced the viral titer of RSV A2 or IAV PR8 in a BALB/c infection model. Importantly, we further established a simultaneous RSV/IAV coinfection model to investigate the antiviral activity of VV251. Oral administration of VV251 once daily significantly inhibited viral replication and decreased the mortality of RSV/IAV-coinfected mice. Our findings establish VV251 as a broad-spectrum drug candidate for the treatment of RSV, IAV, and RSV/IAV coinfection.IMPORTANCERespiratory syncytial virus (RSV) and influenza virus are the two predominant causative agents of acute respiratory tract infections, leading to a substantial number of hospitalizations and thousands of deaths annually. The cost of treating disease caused by infection with RSV and influenza viruses is a huge financial burden on the world. We have identified a nucleotide analog with favorable pharmacokinetic properties and antiviral activity against RSV and influenza A virus (IAV) during mono- or coinfection in a mouse model. This compound has the potential to be used for the treatment of RSV, IAV, and RAV/IAV coinfection.
Zhang et al. (Tue,) studied this question.