MOLECULAR MODELING AND DOCKING OF PHLEBOVIRUS PROTEINS IN LEISHMANIASIS COINFECTION

Introduction. Phleboviruses (Family Phenuiviridae) are circular tri-segmented RNA viruses of clinical importance causing human diseases. Phleboviruses are known to be transmitted to humans by arthropods. The actual knowledge about the biology of this group comes mainly from the Phleboviruses presented in the Old World, such as the Rift Valley and Toscana Virus. One of the main virulence factors is the non-structural protein NSs that interfere with various cellular signaling pathways and reduce the expression of Type I Interferons. Our project looks for two Phlebovirus found in Brazil, the Icoaraci virus (NCBI ID:426790) and Viola pantanalense virus (NCBI ID:2182586). Both should causes coinfection with leishmaniasis, in fact Viola was found in Lutzomyia sandflies in the north of Pantanal and Icoaraci was detected in Nectomys rodents, which are both commonly associated with Leishmania ( Leishmania amazonensis) reservoirs. Objective. The main objective of this project is the characterization of the non-structural proteins (NSs) of phleboviruses using molecular modeling, molecular docking and phylogenetic analysis, aiming to discover how they can interact with the human proteins and their possible immune system evasion mechanism. Materials and Methods. Computational programs are used to create 3D models through artificial intelligence (AlphaFold), looking for protein-protein molecular docking analysis (Hex). Docking is used to investigate how the NSs protein can interact with the target host proteins. Additionally, phylogenetic studies (Mega and FigTree) are applied in order to compare the sequences to other similar viruses already cataloged. This comparative study is used to understand if our modeled NSs proteins can interact with the immune system in the same way as similar viruses. Results and Discussion. Since NSs proteins are poorly conserved, it was necessary to characterize structurally these proteins of the new world Phleboviruses and investigate their potential interaction with human cells. Models were created for Viola and Icoaraci using the AI of AlphaFold, further, these models have been passed on programs to improve their quality. Our studies reveal new characteristics of NSs from the local virus that will be used to increase our knowledge about infection and coinfection with other pathogens like Leishmania. Actually, using docking and phylogenetics, we have start investigate the interactions between the viruses NSs and the immune system proteins like Sequestosome-1 (uniprot:Q13501) and P62GTF2H1(uniprot:P32780).

This work was supported by CNPq.