Crystal structure of the NS3 helicase of tick-borne encephalitis virus

Tick-borne encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus in Flaviviridae. It can cause the server infectious diseases named tick-borne encephalitis (TBE), which is characterized by paralysis and epilepsy. However, no effective treatment for TBE has been developed targeting TBEV. The NS3 helicase from TBEV plays an essential role in viral replication, which makes it an important target for drug design. In this study, the crystal structure of TBEV NS3 helicase has been determined to the resolution of 2.14 Å. Subsequent alignment with homologous structures reveals that the NTP binding site and RNA-binding sites are located in motifs Ⅱ and Ⅵ of NS3 and the critical residues for binding are conserved across species in the genus, while the distinct conformation transition implies that the TBEV helicase need a different local rearrangement. This study demonstrates the key atomic-level features of TBEV helicase and provides basis for the design of antiviral drugs targeting TBEV helicase. •Tick-bone encephalitis virus causes human central nervous system infections.•The helicase unwinds double-stranded RNA to trigger polymerase synthesis of RNA.•It has a nucleotide 5′-triphosphatase and a 5′-terminal RNA triphosphatase activity.•The helicase is a potential drug target against virus to develop inhibitors.