Ensemble Docking of FDA‐Approved and Peruvian Phytochemicals Against Monkeypox Virus Telomere‐Binding Protein

ABSTRACT Monkeypox is a reemerging zoonotic disease that has been spreading worldwide. Different approaches are being conducted to find effective treatments for this disease. To accelerate therapeutic discovery, we propose telomere‐binding protein (TBP) as a potential drug target because of its important role during virus maturation. Using computational biology and biophysics techniques, the MPXV TBP was modeled, and a library of FDA‐approved drugs and phytocompounds was screened using a rigorous ensemble docking protocol; conformational sampling was enhanced by enumerating, for each ligand, ionization states, tautomerism, and ring conformations. Our results present a new approach to drug selection against MPXV, with six potential inhibitors: CHEMBL3894860, CHEMBL461101, CHEMBL2103870, PNSC125, PNSC305, and PNSC123, which can be taken as lead compounds for experimental testing, for example, in plaque reduction assays and qPCR in MPXV‐infected cells to determine EC50, CC50, and selectivity index (SI) values.