Dengue virus type 2 non-structural protein 2B-3 protease (DENV2 NS2B-NS3pro)

The DENV2 NS2B-NS3 protease is a critical enzyme complex of the Dengue virus serotype 2, composed of the N-terminal serine protease domain of non-structural protein 3 (NS3) and its essential cofactor, non-structural protein 2B (NS2B) [2, 3]. This complex is responsible for the proteolytic cleavage of the viral polyprotein at multiple junctions, a process essential for the maturation of viral proteins and subsequent viral replication and assembly [6, 13]. In addition to its role in the viral life cycle, the protease facilitates immune evasion by cleaving host proteins involved in the innate immune response, such as STING [3, 4]. As an indispensable component for viral propagation, it is considered a high-priority target for the development of direct-acting antivirals [1, 17]. However, therapeutic development is hindered by the enzyme's relatively flat and highly charged active site, which complicates the design of potent small-molecule inhibitors [7, 16]. While several peptidomimetics and repurposed drugs like novobiocin and niclosamide have shown inhibitory activity in preclinical studies, no protease inhibitor has yet been approved for clinical use against Dengue virus [4, 11].

Other names

DENV2 NS2B/NS3 proteaseDengue virus serotype 2 NS2B-NS3 complexNS3 proteaseNS3proDengue virus type 2 serine protease

Inhibition of the NS2B-NS3 serine protease activity, preventing the cleavage of the viral polyprotein and disrupting the viral life cycle [4, 13].