Zika virus non-structural protein 2B-non-structural protein 3 protease (NS2B-NS3) (NS2B-NS3)

The Zika virus (ZIKV) NS2B-NS3 protease is a heterodimeric enzyme complex essential for the viral life cycle. It consists of the N-terminal domain of the non-structural protein 3 (NS3), which contains the catalytic triad (His51, Asp75, Ser135), and the non-structural protein 2B (NS2B), which acts as an indispensable cofactor for protease activity and membrane anchoring [5, 13]. The primary biological function of this serine protease is to cleave the viral polyprotein precursor into individual functional structural and non-structural proteins, a process required for viral maturation and replication [6, 15]. Beyond its role in replication, the protease also contributes to the evasion of the host's innate immune response by cleaving cellular signaling proteins [1, 5]. Due to its critical role in the pathogenesis of Zika virus infection, including its association with microcephaly and Guillain-Barré syndrome, the NS2B-NS3 protease is a major target for antiviral drug development [3, 9]. Current therapeutic strategies focus on both orthosteric inhibitors that bind the active site and allosteric inhibitors that disrupt the NS2B-NS3 interaction [7, 10]. However, achieving high selectivity over human host proteases and ensuring drug delivery to the central nervous system and developing fetus remain significant challenges [1, 18].

Other names

Zika virus proteaseNS2B-NS3proZIKV serine proteaseNS2B-NS3 complex

Competitive inhibition of the protease active site (orthosteric) and non-competitive inhibition via the allosteric site to disrupt cofactor-protease interaction.