In summary, UBA1-NS5 interaction plays a significant role during flavivirus replication, and constitutes an attractive target for antiviral strategies

Treatment of infected cells with UBA1 inhibitors, including TAK243 which is being clinically trialled against other human diseases, showed an antiviral effect

UBA1 knockdown restricted Zika (and Usutu) virus replication. UBA1 overexpression led to significant increases in virus titres and viral protein levels. These data supported a proviral role for UBA1

We identified host UBA1, the main E1 enzyme participating in the ubiquitylation cascade, as an interacting factor of different flavivirus NS5s. We confirmed that UBA1 and NS5 colocalise in Zika-infected cells