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

Ongoing identification of cases of nCoV 3, 22 suggests continuing introduction of the virus to humans in the Middle East from an unknown source. Given the genetic relationship of hCoV-EMC/ 2012 to other bat coronaviruses 5 , one can speculate that bats may be the reservoir of this virus; however, additional host species should be considered. With documented human-to-human transmission in close contact situations, and the first documented mild case 22 , there is a real concern that we could be observing the 'tip of the iceberg' and perhaps the start of an epidemic. Regardless, with a 65% case-fatality rate despite intensive medical intervention, therapeutic strategies are urgently needed. Despite the significant increase in research on coronaviruses since the discovery of SARS-CoV in 2003, there is no definitive antiviral or therapeutic treatment for coronavirus infections in humans. Pegylated interferon-a was shown to be an effective prophylactic treatment against infection with SARS-CoV in cynomolgus macaques, but was less effective when administered post exposure 23 . No other therapeutics have been tested for antiviral activity against SARS-CoV in a higher order animal model. In the SARS-CoV mouse model, poly IC:LC 24 and mDEF201 (an adenovirus expressing mouse IFN-a) 25 can protect mice from lethal disease; however, neither of these approaches yields an immediate therapeutic for use in humans. Poly IC:LC has been tested in numerous clinical trials, but is not currently approved for treatment of any human disease. Adenovirus-based therapy has multiple complicating factors, such as pre-existing immunity, that have not been adequately addressed, nor is it approved for use in humans 26 .