Dengue virus nonstructural protein 3–nonstructural protein 4B protein–protein interaction (NS3–NS4B interaction)

The Dengue virus nonstructural protein 3–nonstructural protein 4B protein–protein interaction refers to the essential, direct physical interaction between NS3 and NS4B, two viral nonstructural proteins within the flavivirus replication complex anchored to the endoplasmic reticulum membrane[1][2][3]. NS3 is a multifunctional enzyme with protease and helicase activities; NS4B is an integral membrane protein involved in virulence and in the regulation of host immune responses. The interaction between NS3 (specifically its helicase subdomains) and cytoplasmic regions of NS4B modulates the unwinding of viral RNA, facilitating efficient viral RNA synthesis and assembly of the replication complex[1][2][3]. Disrupting this interface potently inhibits Dengue virus replication, making it an attractive therapeutic target, as demonstrated by the drug JNJ-1802, which blocks this interaction and shows broad-spectrum efficacy against all four Dengue virus serotypes in preclinical and clinical studies[5]. The NS3–NS4B protein–protein interaction is thus a validated therapeutic target in the context of Dengue virus infection.

Other names

NS3/NS4B interactionNS3–NS4B interfaceNS3 helicase–NS4B interactionDengue virus protein–protein interaction (NS3–NS4B)

Inhibition of Dengue virus replication by blocking the NS3–NS4B protein–protein interaction, thereby disrupting the viral replication complex and inhibiting RNA synthesis