A study of drug candidates derived from pleconaril for inhibiting coxsackievirus B3 (Cvb3) by ADMET, molecular docking, molecular dynamics and retrosynthesis

Abstract

In the light of the serious diseases attributed to it, there is an urgent and inescapable need to hunt for antiviral medications for Coxsackievirus B3 (CVB3). The current study looked at four drug candidates (P1–P4) derived from pleconaril, which has antiviral activity against CVB3. According to Lipinski's guidelines, two candidates P3 and P4 can be considered drugs based on the results obtained after evaluating the physicochemical and ADMET properties. The high antiviral activity of these two candidates (pIC₅₀ = 11.063 for P3 and pIC₅₀ = 9.580 for P4), with reference to a control compound (MA: pIC₅₀ = 8.523), was explained by different parameters generated after optimizing their geometries employing the Gaussian09 program suite with the hybrid density functional B3LYP and 6-31G(d,p) basis sets, molecular docking analysis (ΔG (Gibbs energy), FF (full fitness) bonding modes) using the SwissDock server and the molecular dynamics (MD) analysis. The principle of retrosynthesis allowed us to draw a path for the synthesis of these drug candidates. This study may add more valuable and useful information to optimize new pleconaril derivatives.