Interferon-α2b and ribavirin treatment improves outcome in MERS-CoV-infected rhesus macaques

Falzarano, Darryl; de Wit, Emmie; Rasmussen, Angela L.; Feldmann, Friederike; Okumura, Atsushi; Scott, Dana P.; Brining, Doug; Bushmaker, Trenton; Martellaro, Cynthia; Baseler, Laura; Benecke, Arndt G.; Katze, Michael G.; Munster, Vincent J.; Feldmann, Heinz

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern – causing severe respiratory illness with 97 confirmed cases and 46 deaths(1). Therapeutic interventions have not been evaluated in vivo, thus patient management relies exclusively on supportive care, which given the high case-fatality rate is not highly effective. The rhesus macaque is the only known disease model for MERS-CoV, developing an acute localized-to-widespread pneumonia with transient clinical disease(2,3) that recapitulates mild-to-moderate human MERS-CoV cases(4,5). The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro(6); therefore, this strategy was initiated 8 h post-infection in the rhesus macaque model. Treated animals did not develop breathing abnormalities and showed no-to-very mild radiographic evidence of pneumonia. Moreover, treated animals showed reduced levels of systemic (serum) and local (lung) proinflammatory markers in addition to reduced viral genome copies, altered gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic, IFN-α2b and ribavirin should be considered for management of MERS-CoV cases.