Dengue Virus NS3–NS4B Interaction (NS3-NS4B Interaction)

The interaction between the dengue virus non-structural proteins NS3 and NS4B is a critical component of the viral replication complex (RC), which forms on the endoplasmic reticulum (ER) membrane in infected cells. This protein-protein interaction is essential for efficient viral RNA replication and represents a promising target for antiviral drug development. NS3 functions as both a protease and an RNA helicase, while NS4B is an integral membrane protein involved in modulating host immune responses, remodeling ER membranes, and regulating the activity of other viral proteins within the RC. Targeting this interface has been validated as an antiviral strategy, with small molecules like JNJ-1802 showing efficacy in preclinical models by disrupting or blocking this protein-protein contact. Key regions involved include helicase subdomains 2 & 3 of NS3 and the cytoplasmic loop/N-terminal residues of NS4B.

Disrupts NS3-NS4B interaction, inhibiting viral RNA replication