In Silico Evaluation of Selective HDAC6 Inhibitors J27820 and J22352 Against Zika Virus Proteins: Molecular Docking and Dynamics Insights

Abstract

The Zika virus (ZIKV) is classified as a type of the Flavivirus family, which includes various other significant viruses characterized by positive-sense, single-stranded RNA genomes. ZIKV is primarily transmitted to humans via mosquito vectors. While ZIKV infections are often asymptomatic, they can also result in mild flu-like symptoms or severe complications, posing a considerable threat to human health. Several studies have demonstrated that histone deacetylase 6 (HDAC6) inhibitors exhibit antiviral activity against the Zika virus. The current study employs computational chemistry and various in-silico techniques, including molecular docking, ADMET predictions, and molecular dynamics simulations. Initially, the pharmacokinetic and physicochemical properties of J27820 were assessed using ADMET analysis. The therapeutic potential of compounds J22352 and J27820 against three Zika virus (ZIKV) proteins (5H4I, 5TFR, and 6THV) was evaluated using molecular docking simulations. These simulations indicated that the studied compounds exhibited the highest binding affinities and strong interactions with the target proteins. To further assess the stability of the complexes and their interactions over time, 100 ns molecular dynamics simulations were performed. The results of this study highlight the significant advantages of J27820 and J22352, emphasizing their potential for targeted inhibition and promising opportunities for developing effective antiviral therapies against the Zika virus.