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

Gervacio-Villarreal E.; Ropón-Palacios G.; Sancho C.; Pérez-Silva J.; Otazu K.; Olivos-Ramirez G.E.; Vega-Chozo K.; Ramirez-Díaz Y.L.; Chenet-Zuta M.E.; Aguila I.N.D.; Flores M.D.L.C.; Aguiar C.; Camps I. · ChemistrySelect (2026) · DOI: 10.1002/slct.202504269

Resumen

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.

Instituciones: Universidad Peruana Cayetano Heredia; Universidad Nacional de la Amazonía Peruana; Universidad Nacional Tecnológica de Lima Sur