Dengue virus serotype 2 capsid protein (DENV2C)

The Dengue virus serotype 2 capsid protein (DENV2C) is a vital structural protein that facilitates the assembly and encapsidation of the viral RNA genome into a mature nucleocapsid. It exists as a highly basic homodimer with a disordered N-terminal region and four alpha-helices, allowing it to function as an RNA chaperone that promotes the structural rearrangements of the viral genome required for replication (UniProt P12823; NIH PMC7531111). DENV2C also interacts with host lipid droplets and can translocate to the nucleus, where it modulates host cell functions and assists in immune evasion by degrading antiviral factors like EXOC1 (UniProt P12823; MDPI 10.3390/v12070762). In the context of drug development, DENV2C is a promising therapeutic target; small molecules such as ST-148 have been identified to bind the protein's hydrophobic cleft (PNAS 117(30):17992). These inhibitors induce the formation of "kissing tetramers," which stabilizes the capsid structure to the point of preventing the necessary uncoating process during subsequent infection cycles (ASM 10.1128/AAC.01511-12). Despite its potential, challenges include the rapid emergence of resistance mutations and the difficulty of achieving pan-serotype activity across all four Dengue virus serotypes.

Other names

Capsid protein CCore proteinD2CDENV-2 C proteinNucleocapsid protein

Inhibitor-induced tetramerization of the viral capsid (formation of kissing tetramers) which prevents nucleocapsid uncoating and suppresses viral replication.