Inhibition of novel ß coronavirus replication by a combination of interferon-a2b and ribavirin

Falzarano, Darryl; de Wit, Emmie; Martellaro, Cynthia; Callison, Julie; Munster, Vincent J.; Feldmann, Heinz

Supernatants were collected on days 1, 3 and 5 post-infection and subsequent analyses of viral loads (viral RNA) and titers were performed. Peak viral loads and infectious virus were recovered from day 3 samples; therefore, this time point was used for subsequent analysis. Supernatants collected on day 5 frequently had lower viral loads and titers than samples collected on day 3, likely due to extensive CPE. As such, day 5 samples were not included in the analyses. A dose dependent reduction in genome copies was observed for IFN-a2b treatment with a 0.53-log reduction in viral loads at 500 U/ml reaching a 1.84-log reduction at 5000 U/ml (Figure 2A) . A dose dependent reduction in viral loads was also observed for ribavirin treatment, with a 0.82-log reduction at 200 mg/ml reaching a 2.04-log reduction at 2000 mg/ml ( Figure 2B ). Importantly, a corresponding decrease in infectious virus was also observed as a result of IFN-a2b or ribavirin treatment. A 0.57-log reduction in virus titer occurred at 500 U/ml IFN-a2b, increasing to a 1.31-log reduction at 5000 U/ml IFN-a2b ( Figure 2C ). For ribavirin, a 1.24-log reduction in virus titer was observed at 100 mg/ml, reaching a 4.05-log reduction at 2000 mg/ ml ( Figure 2D ).