Discovery of small molecule antivirals targeting tick-borne encephalitis virus

Tick-borne encephalitis (TBE) is an infectious disease common for Northern Eurasia and caused by the tick-borne encephalitis virus (TBEV) from the Flavivirus genus. Usually, TBEV infection starts after the bite of a TBEV-infected tick, but some of TBE cases are caused by consuming unpasteurized dairy milk and milk products containing TBEV. Currently, the main way of preventing TBEV infection is vaccination. There are six vaccines in use over the world, all of them are based on the whole inactivated. Post-onset TBE treatment is usually symptomatic and supportive, as no directly acting small molecule antivirals are approved. Therefore, discovery and development of anti-TBEV drugs and treatment strategies are of urgent need. In this chapter, we present an overview and analysis of efforts and strategies in discovery of small molecule compounds inhibiting the reproduction of TBEV. Phenotypic and target-based in vitro and in silico screening, drug and privileged structure repurposing approaches, as well as current advances in monoclonal antibody design are discussed in details.