Exploring Peptide‐Based Models for Zika Fever: An In‐Silico Investigation

Abstract Zika fever is a global health concern that affects 86 countries and there are no specific drugs or vaccines available. In this regard, this study utilized in silico methods to assess the biological properties of dipeptides and peptide dendrimers against the Zika virus (ZIKV). Docking simulations were performed in GOLD software. Dynamic simulations were carried out in 500 ns using GROMACS software and MM/GBSA calculations were performed to assess the predicted ligand bind affinity. The pharmacokinetic properties of the models were analyzed using ADMETlab platform. Peptide dendrimers outperformed dipeptides in docking simulations (peptide dendrimer 7 , top score: 46.48 versus dipeptide 6 , top score: 37.44). Binding affinity was favored by specific structural features, such as basic and hydrophobic moieties. However, dipeptides showed superior pharmacokinetic profiles in ADMET analysis. Dipeptides 6 and 7 (−33.22 and −32.08 kcal/mol, respectively) and peptide dendrimers 1, 4, and 10 (−41.21, −19.10, and −32.08 kcal/mol, respectively) have favorable binding affinities and could be potential biological active compounds. Peptide dendrimers, especially 10 , showed promising hydrogen bond patterns. These findings require further experimental evaluation to support their significance. Therefore, this work highlights the potential of peptide‐based compounds as an interesting scaffold for Zika fever drug development.