Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin

Abstract

The identification of a novel β coronavirus, nCoV, as the causative agent of severe respiratory illness in humans originating in Saudi Arabia, Qatar and Jordan has raised concerns about the possibility of a coronavirus pandemic similar to that of SARS-CoV. As a definitive treatment regimen has never been thoroughly evaluated for coronavirus infections, there is an urgent need to rapidly identify potential therapeutics to address future cases of nCoV. To determine an intervention strategy, the effect of interferon-α2b and ribavirin on nCoV isolate hCoV-EMC/2012 replication in Vero and LLC-MK2 cells was evaluated. hCoV-EMC/2012 was sensitive to both interferon-α2b and ribavirin alone in Vero and LLC-MK2 cells, but only at relatively high concentrations; however, when combined, lower concentrations of interferon-α2b and ribavirin achieved comparable endpoints. Thus, a combination of interferon-α2b and ribavirin, which are already commonly used in the clinic, may be useful for patient management in the event of future nCoV infections.

Middle East Respiratory Syndrome

“…In vitro, ribavirin showed a reduction in MERS-CoV replication, but the concentrations required to achieve beneficial effects were higher than what is achievable in humans. Therefore, the risk is likely to exceed the possible benefit when ribavirin is used as a monotherapy (51). In addition, rhesus macaque models showed that a combination of INF-α2b and ribavirin improved clinical outcomes and reduced the severity of the illness.…”

What are our pharmacotherapeutic options for MERS-CoV?

“…In vitro studies showed that ribavirin and interferon exhibit anti-MERS-CoV activity [11]. In vitro activity of interferon was further enhanced by the addition of ribavirin [30]. Recently, animal studies utilizing Rhesus Macaque monkeys infected with MERS-CoV were published [31][32][33].…”

The Most Effective Therapeutic Regimen for Patients with Severe Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection

“…It is possible the reason for this reactivation is the fading of the effect of the last dose of PEG-INF α2b which was administered ten days before, resulting in the patient receiving ribavirin monotherapy for three days. Even though this reactivation seemed to be of little clinical significance, it may indicate that monotherapy with lower doses of ribavirin is not sufficient to inhibit the replication of MERS-CoV, therefore, supporting the proposed synergistic effect of PEG-IFN α and ribavirin [4].…”

“…This was based mainly on the potential harmful side effects of the combination. In addition, the use of ribavirin alone for the management of MERS-CoV infection was also believed to be associated with an unfavorable safety profile since high doses of the drug were assumed to be needed to approach the required inhibitory concentration in vivo [4].…”