Structural bioinformatics-based targeting of Epstein-Barr virus BPLF1 deubiquitinase activity against EBV infection...

We screened an in-house library of ~ 900 natural and naturally derived compounds to identify potential inhibitors targeting the BPLF1 deubiquitinase of Epstein-Barr virus, a significant regulator of the NF-κB signaling pathway and viral DNA replication. The virtual screening results 11 compounds demonstrated substantial binding affinities with docking scores ranging from - 6.56 kcal/mol to -8.95 Kcal/mol. Out of these, five compounds (C4, C5, C6, C7, and C11) showed desirable drug-like characteristics, favorable pharmacokinetic properties with no toxicity, and non-allergenicity, and were thus considered applicable candidates for further investigation. Their toxicity was evaluated using MTT assays on BJ human cell lines, where compounds were found to be safe and showed no effect on cell viability at a concentration of 30 µM (11.24% to 34.245%). Interestingly, the DUB activity of BPLF1 was considerably reduced by all five compounds, with potent inhibitory effects demonstrated by their IC₅₀ values (C4 = 5.73 ± 0.16 µM, C5 = 9.47 ± 0.13 µM, C6 = 3.59 ± 0.10 µM, C7 = 14.32 ± 0.32 µM and C11 = 15.76 ± 0.12 µM). Compound C6 showed the strongest inhibition, suggesting its effective antiviral potency against EBV by inhibiting its deubiquitinase activity. These findings open the way for future research into potential drugs to fight EBV and other herpesviruses.

The online version contains supplementary material available at 10.1007/s13205-026-04792-1.