Evaluating the Antiviral Potential of Polyherbal Formulation () Against Monkeypox Virus: Targeting E5, Poxin, and DNA Polymerase Through Multifaceted Drug Discovery Approaches.

The recent reemergence of the monkeypox pandemic in non-endemic regions has raised serious concerns regarding the possibility of a global outbreak. The study employed various modules of the Schrodinger suite through Maestro V 14.1 for molecular docking, MD simulations, MM-GBSA, and FMO. To explore the drug potential of against the key proteins of the Mpox virus: E5, poxin, and DNA polymerase, a total of 982 chemical constituents belonging to this herbal formulation were investigated. The molecular docking studies revealed that chlorogenic acid, chebulic acid, rosmarinic acid, and citric acid had high binding affinities for E5, with docking scores of -13.3289, -11.3933, -9.8999, and -9.59471 kcal/mol, respectively. Likewise, caffeic acid, citric acid, and plumbagic acid have good binding affinities for poxin with docking scores of -8.49023, -6.80386 and -5.91719 kcal/mol, respectively. Plumbagic acid and delphinidin have considerable binding affinities for DNA polymerase with docking scores of -7.57867 and -7.55301 kcal/mol, respectively. In the MD simulation, chlorogenic acid, chebulic acid, citric acid, and rosmarinic acid exhibited remarkable stability with strong binding affinities for the E5, poxin and DNA polymerase. We further explored the stability of the E5 complexes by calculating the binding free energy every 20 ns for 100 ns. The ΔG bind values of chlorogenic acid, chebulic acid, and rosmarinic acid were 61.10, 78.14, and 75.49 kcal/mol at 0 ns. Hence, the research suggests that this formulation has antiviral potential against Monkeypox and can be used to inhibit viral replication in hosts and boost the antiviral immune response.