Structural Motifs and Spatial Structures of Helicase (NS3) and RNA-Dependent RNA-Polymerase (NS5) of a Flavi-Like Kindia Tick Virus (Unclassified Flaviviridae )

— Kindia tick virus (KITV) is a novel, segmented, unclassified flavi-like virus of the Flaviviridae family. This virus is associated with ixodes ticks and is potentially pathogenic to humans. The main goal of this work was to search for structural motifs of viral polypeptides and to model the 3D structure of the NS3 and NS5 viral proteins of the multicomponent flavi-like KITV. Materials and methods. Genome-wide sequences of KITV, Zika, dengue, Japanese encephalitis, West Nile, and yellow fever viruses from the GenBank database were used. Bioinformatics analysis was performed using the AlphaFold2, RCSB PDB, UCSF Chimera, NCBI BLAST, MOTIF Search, Protomenal, Unipro UGENE, and ESPript software package. Results. Analysis of the VP1–VP3 structural proteins of the KITV showed that they have no analogues with currently known viral proteins. Spatial models of two viral nonstructural NS3 and NS5 proteins of the KITV have been obtained. These models had a high level of topological similarity to the NS3 and NS5 proteins of the tick-borne encephalitis and dengue viruses. The domains of methyltransferase and RNA-dependent RNA-polymerase were found in the NS5 KITV and this was also represented by subdomains of fingers, palm, and thumb and motifs A–F. The helicase domain and its main structural motifs I, Ia, II, III, IV, IVa, V, and VI were identified in NS3 KITV. However, the serine protease domain typical for NS3 flaviviruses was not detected. The highly conserved motives 3–7 amino acids in length, typical for unsegmented flaviviruses, were detected in the NS3 and NS5 KITV. Also, eight amino acid substitutions were detected for KITV/2018/1 and KITV/2018/2, five of which are localized in alpha-helix and three in loops of nonstructural proteins. Conclusions. Nonstructural proteins of segmented flavi-like KITV have structural and functional similarities with unsegmented flaviviruses. This confirms their possible evolutionary and taxonomic relationships.