Dengue virus serotype 3 capsid protein (DENV-3 C)

The Dengue virus serotype 3 capsid protein (C protein) is a small, highly basic structural protein essential for the viral life cycle. Its primary role is to package the positive-sense single-stranded RNA genome into a nucleocapsid, which is then enveloped by a lipid bilayer containing the envelope (E) and membrane (M) proteins (UniProt: A0A7D8HXX1). Beyond its structural role, the C protein acts as an RNA chaperone and interacts with host cell components, most notably lipid droplets and very low-density lipoproteins (VLDL), to facilitate viral assembly and replication (Faustino et al., 2015, NIH: PMC4516019). It also plays a role in immune evasion by antagonizing host innate immune responses and serving as a signal peptide for the non-structural protein NS4B (UniProt: Q7T4M8). As a therapeutic target, the C protein is attractive due to its critical role in both the assembly of new virions and the uncoating of the viral genome during entry (Byrd et al., 2013, PubMed: 23114750). Small molecules like ST-148 have been shown to inhibit replication by inducing aberrant capsid self-interaction and tetramerization, while peptide leads like pep14-23 target the protein's interaction with host lipid droplets (Xia et al., 2020, PubMed: 32661167). However, challenges remain in developing pan-serotype inhibitors that can overcome the high genetic variability of the four dengue serotypes and the rapid emergence of resistance mutations, such as the S34L substitution (Byrd et al., 2013).

Other names

Capsid protein CCore proteinC proteinDENV3 CDengue virus type 3 capsid protein

Inhibition of capsid-lipid droplet interaction and enhancement of capsid self-interaction to perturb viral assembly and disassembly.