Intrinsic disorder in flaviviral capsid proteins and their role in pathogenesis

A high level of disorder in many viral proteins is a direct consequence of their small genomes, which makes interaction with multiple binding partners a necessity for infection and pathogenicity. A segment of the flaviviral capsid protein, also known as the molecular recognition feature (MoRF), undergoes a disorder-to-order transition upon binding to several protein partners. In order to understand their role in pathogenesis, the MORFs were identified and their homology was studied. Despite the lack of sequence similarities, the docking studies of Cs with the host proteins indicate conserved interactions involving MORFs across members of the phylogenetic subclades. Additionally, it was observed from the protein-protein networks that some MoRFs preferentially bind proteins that are involved in specialized functions such as ribosome biogenesis. The findings point to the importance of the MoRFs in the flaviviral life cycle, with important consequences for disease progression and suppression of the host immune system. Potentially, they might have impacted the way flaviviruses evolved to infect varied hosts using multiple vectors. ### Competing Interest Statement The authors have declared no competing interest.