Dengue virus non-structural protein 4B (NS4B)

Dengue virus non-structural protein 4B (NS4B) is a small, highly hydrophobic integral membrane protein (approximately 27 kDa) localized to the endoplasmic reticulum (ER) of host cells [PMID: 24962228]. It is a critical component of the viral replication machinery, acting as a scaffold that facilitates the assembly of the replication complex by interacting with other non-structural proteins such as NS3 and NS5 [PMID: 30045991]. Beyond its role in RNA synthesis, NS4B is a potent antagonist of the host's innate immune system, specifically blocking the interferon-alpha/beta signaling pathway to prevent the establishment of an antiviral state [PMID: 15709000]. Because NS4B is essential for the viral life cycle and is relatively conserved across all four Dengue virus serotypes, it has become a high-priority target for direct-acting antivirals [PMID: 34616031]. Clinical-stage inhibitors like JNJ-1802 (Mosnodenvir) target NS4B to disrupt viral replication and are being evaluated for both the prevention and treatment of Dengue infections [Source: Johnson & Johnson, Nature 2021].

Other names

Non-structural protein 4BNS4B proteinDENV NS4BDengue virus NS4B

Inhibition of the viral replication complex formation by disrupting NS4B self-association and its interaction with other non-structural proteins, thereby preventing viral RNA synthesis.