Dengue virus serotype 4 capsid protein (DENV-4 C)

The Dengue virus serotype 4 capsid protein (DENV-4 C) is a vital structural component of the DENV-4 virion, primarily responsible for encapsidating the viral positive-sense single-stranded RNA genome (UniProt: P09866). It functions as a homodimer, characterized by a highly basic N-terminal region that binds RNA and a hydrophobic internal fold that facilitates interaction with host lipid droplets and the viral envelope (PubMed: 15016363). This interaction with lipid droplets is crucial for viral replication and assembly within the host cell, serving as a reservoir for the protein before it moves to the endoplasmic reticulum (PubMed: 21994453). In the context of disease, DENV-4 is one of the four distinct serotypes that cause Dengue fever, which can progress to life-threatening Dengue Hemorrhagic Fever or Dengue Shock Syndrome (WHO, 2023). The C protein is essential for the formation of the nucleocapsid; without its proper function, the virus cannot produce infectious progeny or spread to new cells. As a therapeutic target, the C protein is targeted by experimental small molecules like ST-148, which aim to disrupt the assembly of the nucleocapsid or its interaction with the viral membrane (PubMed: 23133214). These inhibitors often bind to the hydrophobic pocket of the capsid dimer, preventing the necessary conformational changes or protein-protein interactions required for viral maturation. Developing drugs against this target is challenging due to the high mutation rate of the virus and the necessity for the drug to be effective across all four Dengue serotypes to avoid treatment failure (PubMed: 25588510).

Other names

Capsid protein CCore proteinDENV4 C proteinStructural protein C

Inhibition of viral nucleocapsid assembly and disruption of capsid-membrane interactions by binding to the hydrophobic pocket of the capsid homodimer.