West Nile Virus non-structural protein 2B-non-structural protein 3 protease (WNV NS2B-NS3pro)

The West Nile Virus (WNV) non-structural protein 2B-non-structural protein 3 protease (NS2B-NS3 protease) is a vital enzyme complex required for the replication and maturation of the West Nile Virus [1, 2]. It is a heterodimer consisting of the N-terminal serine protease domain of the NS3 protein and a central hydrophilic domain of the NS2B protein, which acts as an essential cofactor for catalytic activity [3, 6]. The protease's primary biological role is to cleave the viral polyprotein at specific sites to release functional structural and non-structural proteins, a process that is essential for the assembly of new infectious virions [5, 13]. As polyprotein processing is a mandatory step in the viral life cycle, this protease is considered a high-priority therapeutic target for the development of antivirals to treat West Nile fever and its severe neuroinvasive forms, such as encephalitis and meningitis [2, 9]. Currently, there are no FDA-approved drugs targeting this enzyme, and drug discovery efforts face challenges due to the shallow, solvent-exposed nature of the active site and the need for high selectivity to avoid inhibiting host proteases [1, 16]. Research is ongoing into small-molecule inhibitors, peptidomimetics, and allosteric modulators that can effectively block viral replication while maintaining a favorable safety profile [4, 14].

Other names

WNV NS2B-NS3 proteaseWNV NS2B-NS3proWest Nile Virus NS2B-NS3 serine proteaseWest Nile Virus NS2B-NS3 complexWest Nile Virus NS2B-NS3 fusion proteinNS2B-NS3 protease

Protease inhibition