Dengue virus polyprotein (DENV polyprotein) (DENV polyprotein)

The Dengue virus polyprotein is the precursor for all ten proteins of the Dengue virus (DENV), an RNA virus belonging to the Flaviviridae family [1]. It is cleaved into structural proteins (Capsid, Pre-membrane, and Envelope) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [2]. The Envelope (E) protein is the primary target for vaccine-induced neutralizing antibodies as it mediates viral attachment and fusion with host cells [3]. Non-structural proteins like NS3 and NS5 serve as essential enzymes for viral replication, acting as a protease/helicase and RNA-dependent RNA polymerase, respectively [4]. NS1 is a unique secreted glycoprotein that plays a significant role in immune evasion and the induction of vascular leakage, a hallmark of severe dengue [5]. Therapeutic strategies targeting these antigens include tetravalent vaccines designed to elicit balanced immunity against all four DENV serotypes and direct-acting antivirals that inhibit specific enzymatic functions or protein-protein interactions [6]. A major challenge in targeting DENV antigens is antibody-dependent enhancement (ADE), where sub-neutralizing antibodies can facilitate viral entry into host cells, potentially worsening the disease [7].

Other names

Dengue virus antigensDENV proteinsDengue virus structural and non-structural proteinsDENV polyprotein

Mechanisms include viral neutralization by antibodies (vaccines), inhibition of the NS4B protein to block replication (Mosnodenvir), inhibition of the NS5 RNA-dependent RNA polymerase (Balapiravir), and inhibition of host alpha-glucosidases to prevent proper folding of the Envelope glycoprotein (Celgosivir) [4, 6].