The mpox virus (MPXV), a member of the Poxviridae family, which recently appeared outside of the African continent has emerged as a global threat to public health. Given the scarcity of antiviral treatments for mpox disease, there is a pressing need to identify and develop new therapeutics. We investigated 5715 phytochemicals from 266 species available in IMMPAT database as potential inhibitors for six MPXV targets namely thymidylate kinase (A48R), DNA ligase (A50R), rifampicin resistance protein (D13L), palmytilated EEV membrane protein (F13L), viral core cysteine proteinase (I7L), and DNA polymerase (E9L) using molecular docking. The best-performing phytochemicals were also subjected to molecular dynamics (MD) simulations and in silico ADMET analysis. The top phytochemicals were forsythiaside for A48R, ruberythric acid for A50R, theasinensin F for D13L, theasinensin A for F13L, isocinchophyllamine for I7L, and terchebin for E9L. Interestingly, the binding energies of these potential phytochemical inhibitors were far lower than brincidofovir and tecovirimat, the standard drugs used against MPXV, hinting at better binding properties of the former. These findings may pave the way for developing new MPXV inhibitors based on natural product scaffolds. However, they must be further studied to establish their inhibitory efficacy and toxicity in in vitro and in vivo models.

痘病毒（MPXV）是痘病毒科的一员，最近出现在非洲大陆以外的地区，已成为对公共健康的全球威胁。鉴于mpox疾病的抗病毒治疗方法匮乏，迫切需要确定和开发新的疗法。我们研究了 IMMPAT 数据库中 266 个物种的 5715 种植物化学物质，作为 6 个 MPXV 靶标的潜在抑制剂，即胸苷酸激酶 (A48R)、DNA 连接酶 (A50R)、利福平抗性蛋白 (D13L)、棕榈化 EEV 膜蛋白 (F13L)、病毒核心半胱氨酸蛋白酶(I7L) 和 DNA 聚合酶 (E9L) 使用分子对接。性能最佳的植物化学物质还进行了分子动力学 (MD) 模拟和计算机 ADMET 分析。排名最高的植物化学物质是 A48R 的连翘硫苷、A50R 的红红酸、D13L 的茶素 F、F13L 的茶素 A、I7L 的异松叶碱和 E9L 的特切宾。有趣的是，这些潜在植物化学抑制剂的结合能远低于用于对抗 MPXV 的标准药物布西多福韦和替科维马，这表明前者具有更好的结合特性。这些发现可能为开发基于天然产物支架的新型 MPXV 抑制剂铺平道路。然而，必须进一步研究它们，以确定它们在体外和体内模型中的抑制功效和毒性。