Inhibition of monkeypox polymerase holoenzyme and methyltransferase using bioactive compounds of black tea: a computational approach
摘要
The WHO declared monkeypox a global health emergency due to its rapid spread. In response, the FDA authorized emergency use of the Jynneos vaccine despite its adverse effects, while smallpox antivirals, repurposed for monkeypox treatment, have shown limited efficacy, highlighting the need for better therapeutics that are biocompatible, less toxic, and more accessible. Tea bioactives, known for their antiviral properties, were evaluated using an in silico approach to target viral enzymes: polymerase holoenzyme and methyltransferase. A total of 68 bioactives, mainly polyphenols from tea, were analyzed through molecular docking. Among them, digalloylprocyanidin B2, TSB, and NTF showed the lowest binding energies of -9.6441 kcal mol−1, -9.1740, kcal mol−1, and − 9.1563 kcal mol−1, respectively against the polymerase holoenzyme, while TSA, TF, and TF3 exhibited the binding energies of -10.2649 kcal mol−1, -9.5998 kcal mol−1, and − 9.0857 kcal mol−1, respectively for methyltransferase. The compounds showed stronger binding than reference drugs. MDS (100 ns) using Desmond software showed that top-ranked ligand complexes were more stable than unbound proteins and reference drug complexes. MM-GBSA calculations revealed greater stability with the polymerase holoenzyme than methyltransferase. Further in vitro and in vivo studies are needed to confirm their inhibitory effects.