Modelado molecular de la interacción entre las proteínas virales del FPLV y proteínas de membrana de células gastrointestinales de gato doméstico (Felis catus)

Abstract

Feline panleukopenia (FPL) is a viral disease caused by the feline panleukopenia virus (FPLV), whose capsid is mainly composed of proteins VP1 and VP2, which are involved in tropism, antigenicity, and the interaction with the feline transferrin receptor (TfRf). Despite its clinical and epidemiological relevance, gaps remain in the understanding of the structural determinants that mediate this interaction. The aim of this work was to analyze, through computational tools, the VP2–TfRf interaction to identify key contacts and conformational patterns with functional relevance. The research was conducted in three phases: (1) a systematic literature review and phylogenetic analysis of VP2, incorporating sequences from FPLV and closely related parvoviruses; (2) three-dimensional modeling and in silico validation of VP1 and VP2, using optimized alignment strategies and template selection; and (3) molecular dynamics simulation of the VP2–TfR1 complex to assess its stability and characterize inter-residue contacts. The results confirm a high structural homology between FPLV and canine parvovirus (CPV), allowing extrapolation of capsid–receptor binding mechanisms. The modeling of VP1 and VP2 yielded high-quality structures, validated by stereochemical and potential energy parameters. Molecular dynamics showed that the VP2–TfR1 complex maintains a stable interface over 100 ns, with persistent contacts and localized conformational changes that favor receptor binding, supporting the hypothesis that localized flexibility in VP2 is key for specific recognition of the TfRf. Taken together, this study provides conceptual and methodological foundations for the design of inhibitors aimed at blocking viral entry and for vaccine optimization. It also demonstrates the value of in silico approaches in structural virology, offering tools to address knowledge gaps on FPLV biology and to support prevention strategies in both domestic and wild felines.