Zika virus NS2B-NS3 serine protease (ZIKV NS2B-NS3pro)

The Zika virus NS2B-NS3 serine protease is a critical enzyme complex required for the maturation and replication of the Zika virus (ZIKV). It is a heterodimer composed of the N-terminal domain of the NS3 protein, which contains the catalytic triad (His51, Asp75, Ser135), and a hydrophilic region of the NS2B protein that serves as an essential cofactor for enzymatic activity (Zhang et al., 2016, Science). The primary biological function of this protease is to cleave the viral polyprotein at specific sites (NS2A/NS2B, NS2B/NS3, NS3/NS4A, and NS4B/NS5) to generate functional non-structural proteins (Li et al., 2016, Nature Communications). In the context of disease, ZIKV infection is linked to severe neurological conditions such as microcephaly in fetuses and Guillain-Barré syndrome in adults; by enabling viral replication, the protease directly contributes to these pathologies (Mlakar et al., 2016, NEJM). As a therapeutic target, the protease is highly attractive because its active site is distinct from most human proteases, though achieving high selectivity remains a challenge. Various small molecules, including repurposed drugs like novobiocin and experimental peptidomimetics, have been investigated for their ability to inhibit the protease and suppress viral load (Yuan et al., 2017, Nature Communications).

Other names

Zika virus NS3 proteaseNS2B-NS3 protease complexZIKV NS2B-NS3 serine proteaseNS2B-NS3pro

Competitive inhibition of the NS3 active site or allosteric disruption of the NS2B-NS3 protein-protein interaction (Zhang et al., 2016).