Joshi Tushar, Priyamvada Priyamvada, Mathpal Shalini, Sriram Suratha, Madaan Shivani, Ramaiah Sudha, Anbarasu Anand
Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology (VIT), 632014, Vellore, Tamil Nadu, India.
Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), 632014, Vellore, Tamil Nadu, India.
J Biol Phys. 2025 May 26;51(1):17. doi: 10.1007/s10867-025-09683-9.
Ebola virus disease (EVD) is an acute life-threatening disease caused by highly pathogenic Ebolavirus (EBOV), with reported case fatality rates reaching 90%. There have been numerous EBOV outbreaks and epidemics since the first outbreak was reported in Africa in 1976. Despite the approval of three vaccines and two monoclonal antibody therapies by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of EVD the urgent need for alternative therapeutic strategies persists. In the present study, we screened a library of 235 phytocompounds derived from Azadirachta indica against the key EBOV viral protein 24 (VP24), VP30, VP35 and VP40 through a random forest-based machine learning model with an accuracy of 84.5%. Initially, 48 compounds were identified as active, and subsequent toxicity assessment refined the selection to a promising candidate, daucosterol. Molecular docking studies indicated that daucosterol exhibited significant binding affinity to all four viral proteins. Subsequent validation through molecular dynamics simulations confirmed the stability of daucosterol protein complexes. These results imply that daucosterol acts as a potential multitarget inhibitor against EBOV proteins and could serve as a promising lead compound for future therapeutic development against EVD.
埃博拉病毒病（EVD）是一种由高致病性埃博拉病毒（EBOV）引起的急性危及生命的疾病，报告的病死率高达90%。自1976年在非洲首次报告埃博拉病毒疫情以来，已经发生了多次疫情。尽管美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准了三种疫苗和两种单克隆抗体疗法用于治疗埃博拉病毒病，但对替代治疗策略的迫切需求依然存在。在本研究中，我们通过基于随机森林的机器学习模型，以84.5%的准确率，对从印楝中提取的235种植物化合物文库进行筛选，针对关键的埃博拉病毒病毒蛋白24（VP24）、VP30、VP35和VP40。最初，48种化合物被鉴定为有活性，随后的毒性评估将选择范围缩小到一种有前景的候选物——胡萝卜苷。分子对接研究表明，胡萝卜苷对所有四种病毒蛋白都表现出显著的结合亲和力。随后通过分子动力学模拟进行的验证证实了胡萝卜苷 - 蛋白质复合物的稳定性。这些结果表明，胡萝卜苷作为一种针对埃博拉病毒蛋白的潜在多靶点抑制剂，有望成为未来治疗埃博拉病毒病的先导化合物。
