Dengue virus NS2B/NS3 serine protease (NS2B/NS3 protease)

The **Dengue virus NS2B/NS3 serine protease** is an essential viral enzyme encoded by dengue virus (DENV), a member of the Flaviviridae family. This protease consists of the NS3 protein, which harbors a trypsin-like serine protease domain at its N-terminus, and the NS2B cofactor, which is required for its full enzymatic activity[1][4]. The NS2B/NS3 protease is responsible for cleaving the viral polyprotein at multiple sites, a critical step in viral replication and maturation[1][5]. Its catalytic triad comprises residues His51, Asp75, and Ser135[1][4]. This enzyme is also involved in evasion of the host innate immune response[4], making it a prime target for new antiviral therapies against dengue infection. Inhibitors such as policresulen, aprotinin, and various designed cyclic peptides have shown efficacy in targeting the NS2B/NS3 protease by blocking its active site or modulating its conformation, thereby suppressing viral replication[2][3][7]. No clinically approved direct-acting antivirals target this protease to date, but it remains a high-priority target for drug discovery due to its indispensable role in the viral life cycle and absence of closely related analogs in humans[4][5]. The main therapeutic challenge lies in achieving high selectivity and overcoming resistance mechanisms linked to mutations in the NS2B region[6][7].

Other names

Dengue virus NS2B-NS3 proteaseDengue NS2B/NS3 proteaseDENV NS2B/NS3 proteaseDENV proteaseNS2B/NS3pro

Competitive inhibition of serine protease active site[2][3]; Inhibition of viral polyprotein cleavage; Suppression of viral replication[4][5]