Comparative study of the antiviral activity of broad-spectrum and enterovirus-specific inhibitors against clinical isolates of enterovirus-D68

Enterovirus-D68 was isolated for the first time in California in 1962 in children with pneumonia and bronchiolitis. Until 2008, the detection of EV-D68 infections has been very rare. Since 2008 EV-D68 got increased attention with different clusters of infections worldwide. In a recent epidemic in the United States, 1.153 people were confirmed with respiratory illness caused by EV-D68, mostly children with asthma or a history of wheezing. The virus also has been associated occasionally with polio-like illness (muscle weakness or paralysis). Moreover, EV-D68 was detected in specimens from 14 patients who died. EV-D68 thus emerged as a considerable global health threat, requiring the development of effective antiviral treatment. To assess the activity of antiviral molecules against EV-D68 a panel of 7 clinical isolates was selected consisting of representative strains of the three major genogroups. The following inhibitors were included in this study: (i) two capsid-binding compounds, pleconaril and pirodavir; (ii) the protease inhibitor rupintrivir; (iii) the host cell-targeting compound enviroxime; and (iv) the broad-spectrum antivirals favipiravir (T-705) and arbidol. Our preliminary results with the 7 clinical isolates reveal that pleconaril and rupintrivir efficiently inhibited in vitro EV-D68 replication. Favipiravir (recently approved in Japan to treat influenza virus infections) and enviroxime also resulted in a clear antiviral effect. On the other hand, pirodavir and arbidol resulted only in a modest inhibitory effect on EV-D68 replication. We will present data on the in vitro anti-EV-D68 activity of this compound-panel against the wider panel of recent EV-D68 isolates.status: publishe