Zika virus non-structural protein 2B-non-structural protein 3 protease I156T mutant (ZIKV NS2B-NS3 protease I156T)

The Zika virus non-structural protein 2B-non-structural protein 3 (NS2B-NS3) protease I156T mutant is a specific variant of the essential heterodimeric enzyme complex required for the maturation and replication of the Zika virus (ZIKV) (NIH, 2022). This complex consists of the N-terminal protease domain of the NS3 protein and its essential cofactor, the NS2B protein, which is required to stabilize the enzyme's active conformation (Lei and Hilgenfeld, 2016). The I156T mutation, located at position 156 of the NS3 protease domain, has been identified as a primary resistance mutation against a novel class of allosteric inhibitors, such as the N-acylsydnone imine compounds IRBM-Z-1 and IRBM-Z-2 (Ontoria et al., 2026). This mutation significantly reduces the binding affinity of these allosteric inhibitors, which normally function by locking the protease in a catalytically inactive, open-like conformation (Ontoria et al., 2026). Biologically, the NS2B-NS3 protease is responsible for cleaving the viral polyprotein into individual functional proteins and also targets host cell proteins like ATG16L1 and eIF4G1 to facilitate immune evasion and viral protein synthesis (NIH, 2018). Because the protease is vital for the viral lifecycle and lacks a direct human homolog, it is a major focus for antiviral drug development, though the emergence of mutants like I156T presents a significant challenge for achieving sustained therapeutic efficacy (NIH, 2022).

Other names

Zika virus NS3 protease I156T mutantZIKV NS2B-NS3pro I156TZika virus non-structural protein 3 I156T mutantZIKV NS2B-NS3 protease resistance mutant

Allosteric inhibition by binding to a pocket that locks the enzyme in an inactive conformation; orthosteric inhibition by binding to the catalytic triad (His51, Asp75, Ser135).