Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil [MMF], lopinavir/ritonavir, and interferon-beta 1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon-beta 1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores down arrow 50.9%-95.0% and down arrow weight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung (down arrow 0.59-1.06 log(10) copies/glyceraldehyde 3-phosphate dehydrogenase [GAPDH]; P<.050) and extrapulmonary (down arrow 0.11-1.29 log(10) copies/GAPDH; P<.050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads (up arrow 0.15-0.54 log(10) copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0-33% (lopinavir/ritonavir-treated and interferon-beta 1b-treated). Lopinavir/ritonavir and interferon-beta 1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used.