Bioinformatic Prediction of Cellular Targets of Aminoestrones through Molecular Docking: Implications for Flavivirus Replication and Cell-to-Cell Transmission.

Abstract

Background: Flaviviruses such as dengue virus and Zika virus rely on host cellular factors to complete their replication cycle. Host proteins involved in cytoskeleton dynamics and vesicular trafficking may represent potential therapeutic targets. Bioactive aminoestrones have shown antiviral activity, although their molecular mechanisms remain poorly understood. Methods: A bioinformatic analysis based on molecular docking was performed to identify potential cellular targets of the aminoestrone compound US2NE102. Three-dimensional structures of Hsp70, Rac1, PAK1, Caveolin-1 and Annexin A2 were obtained from the AlphaFold Protein Structure Database. Docking analysis and cavity identification were performed using CB-Dock2. Physicochemical properties were evaluated using SwissADME. Results: Docking results revealed relevant binding affinities between US2NE102 and several host proteins involved in cytoskeleton regulation and vesicular trafficking. The highest affinities were observed for PAK1 (−10.8 kcal/mol), Annexin A2 (−10.2 kcal/mol) and Hsp70 (−9.2 kcal/mol), followed by Rac1 (−8.6 kcal/mol) and Caveolin-1 (−8.5 kcal/mol). Conclusion: These findings suggest that US2NE102 may act as a multitarget modulator of host proteins involved in flavivirus replication and cell-to-cell transmission, providing a bioinformatic basis for future antiviral strategies.