The recent outbreak of Zika virus (ZIKV) infection has caused global concern due to its link to severe damage to the brain development of foetuses and neuronal complications in adult patients. A worldwide research effort has been undertaken to identify effective and safe treatment and vaccination options. Among the proposed viral and host components, the viral NS2B-NS3 protease represents an attractive drug target due to its essential role in the virus life cycle. Here, we outline recent progress in studies on the Zika protease. Biochemical, biophysical, and structural studies on different protease constructs provide new insight into the structure and activity of the protease. The unlinked construct displays higher enzymatic activity and better mimics the native state of the enzyme and therefore is better suited for drug discovery. Furthermore, the structure of the free enzyme adopts a closed conformation and a preformed active site. The availability of a lead fragment hit and peptide inhibitors, as well as the attainability of soakable crystals, suggest that the unlinked construct is a promising tool for drug discovery.

最近爆​​发的寨卡病毒（ZIKV）感染已引起全球关注，因为它与严重损害胎儿大脑发育和成年患者的神经元并发症有关。为了确定有效和安全的治疗方法和疫苗接种方案，已经进行了一项全球研究。在拟议的病毒和宿主成分中，病毒NS2B-NS3蛋白酶由于在病毒生命周期中的重要作用而成为有吸引力的药物靶标。在这里，我们概述了寨卡蛋白酶研究的最新进展。对不同蛋白酶构建体的生化，生物物理和结构研究为蛋白酶的结构和活性提供了新的见识。未连接的构建体显示出更高的酶促活性，并更好地模拟了酶的天然状态，因此更适合于药物发现。此外，游离酶的结构采用封闭构象和预先形成的活性位点。铅片段命中和肽抑制剂的可用性以及可浸泡晶体的可获得性表明，未连接的构建体是用于药物发现的有前途的工具。