Structural Study Of Tick-borne Encephalitis Virus Helicase

Tick-borne encephalitis virus(TBEV)is a positive-sense single-stranded RNA Flavivirus,which is the pathogen of tick-borne encephalitis(TBE).Patients with severe TBE may suffer from paralysis and epilepsy,and even lose their lives.China is one of the most serious epidemic areas of TBE.Furthermore,with global warming and increased human activities in forest,the endemic areas began to expand,and the incidence of TBE also increased year by year,which endangered public health security seriously.So far,there is no effective treatment for TBE by targeting pathogens.Although vaccines can effectively prevent the disease,the difficulty of prevention is increasing with the expansion of susceptible population.There is an urgent need to discover effective ways to treat TBE by targeting its pathogens.Recently,structural-based antiviral drug design is a research hotspot.The helicase of TBEV plays an irreplaceable role during its replication,and is an important target for drug design.Therefore,we take TBEV helicase for research object,firstly establishing expression system of TBEV helicase.After a series of purification processes,we obtained high-purity samples of TBEV helicase.And then we utilized the research method of protein crystallography,obtaining the crystal of TBEV helicase.Finally,we solved the crystal structure of TBEV helicase with a resolation of 2.1 ?.After structural comparison and analysis with other Flavivirus helicases,we found a possible NTP hydrolysis a site and an RNA binding site for TBEV,together with several conserved amino acid residues,including E291,R463,R466,ect.,that may play an important role.In conclusion,this research reveals the key features of TBEV helicase from the atomic level,and provides potent reference for antiviral drug design targeting TBEV helicase.It will establish foundation to further study of effective treatment of TBE.