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

Given their long history of combined use for treatment of hepatitis C 20,21 , we combined IFN-a2b and ribavirin treatment to determine whether one compound would augment the activity of the other. Combination treatment in Vero and LLC-MK2 cells lowered the threshold at which a decrease in CPE was noted. For Vero cells, this was reduced to 62 U/ml IFN-a2b and 12 mg/ml ribavirin with the absence of CPE at and above 125 U/ml IFN-a2b and 25 mg/ml ribavirin ( Figure 1A ). This represents an 8-and 16-fold decrease in the amount of IFN-a2b and ribavirin, respectively, which is required to achieve the same reduction as either treatment alone. Viral nucleocapsid protein expression was also reduced in a dose dependent manner starting at concentrations of IFN-a2b and ribavirin of 250 U/ml and 50 mg/ml, respectively ( Figure 1B) . The reduction in CPE and nucleocapsid protein expression also correlated with reduced virus genome copies and titers. When IFN-a2b was administered with ribavirin at 551 ratio, there was an additional reduction in the virus titer by 0.4-to 2.16-logs over that of IFN-a2b treatment alone ( Figure 4 ).