Tick-borne encephalitis virus non-structural protein 3 helicase (TBEV NS3h)

The Tick-borne encephalitis virus (TBEV) helicase is a critical enzymatic component of the viral non-structural protein 3 (NS3), playing a central role in the replication cycle of this flavivirus (UniProt P08488). It possesses both NTPase and RNA helicase activities, utilizing the energy derived from ATP hydrolysis to unwind double-stranded RNA intermediates into single strands, which serve as templates for further genomic replication (PDB 5Z82; PMID: 29769354). TBEV is a major cause of human neuroinvasive infections in Europe and Asia, leading to conditions such as meningitis, encephalitis, and long-term neurological sequelae. Given its essential role in viral proliferation and the structural conservation across the Flaviviridae family, the NS3 helicase is a primary target for the development of direct-acting antivirals. While no specific drugs are currently approved for clinical use against this target, research is active in identifying small molecules like ivermectin or suramin that can selectively inhibit its activity without affecting host cellular helicases (Mastrangelo et al., 2012; PMID: 22164239; PMID: 25541765). Effective therapeutic intervention would likely require compounds capable of crossing the blood-brain barrier to address the central nervous system involvement characteristic of the disease.

Other names

TBEV NS3 helicaseTick-borne encephalitis virus NS3 proteinNS3 NTPase/helicaseFlavivirus helicase

Inhibition of the ATP-dependent unwinding of viral double-stranded RNA and suppression of NTPase activity, thereby preventing viral genome replication.