Scholarlink

<p>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&#xa0;kcal/mol to -8.95 Kcal/mol. Out of these, five compounds (<b>C4</b>,<b> C5</b>,<b> C6</b>,<b> C7</b>, and <b>C11</b>) 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 IC<sub>50</sub> values (<b>C4</b> = 5.73 ± 0.16 µM, <b>C5</b> = 9.47 ± 0.13 µM, <b>C6</b> = 3.59 ± 0.10 µM, <b>C7</b> = 14.32 ± 0.32 µM and <b>C11</b> = 15.76 ± 0.12 µM). Compound <b>C6</b> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structural bioinformatics-based targeting of Epstein-Barr virus BPLF1 deubiquitinase activity against EBV infection and in-vitro validation

  • 期刊论文

  • 发表日期：

    2026年5月5日

查看全文
  • Atta Ullah,
  • Saeed Ullah,
  • Najeeb Ur Rehman,
  • Mesaik M. Ahmed,
  • Hanan A. Ogaly,
  • Sobia Ahsan Halim,
  • Ajmal Khan,
  • Ahmed Al-Harrasi

摘要

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.