Sequence, structure and function relationships in flaviviruses as assessed by evolutive aspects of its conserved non-structural protein domains

Flaviviruses are responsible for serious diseases such as dengue, yellow fever, and zika fever. Their genomes encode a polyprotein which, after cleavage, results in three structural and seven non-structural proteins. Homologous proteins can be studied by conservation and coevolution analysis as detected in multiple sequence alignments, usually reporting positions which are strictly necessary for the structure and/or function of all members in a protein family or which are involved in a specific sub-class feature requiring the coevolution of residue sets. This study provides a complete conservation and coevolution analysis on all flaviviruses non-structural proteins, with results mapped on all well-annotated available sequences. A literature review on the residues found in the analysis enabled us to compile available information on their roles and distribution among different flaviviruses. Also, we provide the mapping of conserved and coevolved residues for all sequences currently in SwissProt as a supplementary material, so that particularities in different viruses can be easily analyzed. •Flaviviruses protein domains were analyzed by conservation and coevolution analysis.•Important residues for structure and function of flaviviral proteins were retrieved.•Uncharacterized positions with similar behavior were identified.•Coevolution analysis among domains point NS3 as mostly coevolved with other proteins.