Tang Kang, Sun Qianru, Zeng Jinfeng, Tang Jing, Cheng Peiwen, Qiu Zekai, Long Haoyu, Chen Yilin, Zhang Chi, Wei Jie, Qiu Xiaoping, Jiang Guozhi, Fang Qianglin, Sun Litao, Sun Caijun, Du Xiangjun
School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 510275, PR China; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, PR China; School of Public Health, Guangdong Medical University, Dongguan 523808, PR China.
School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 510275, PR China; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, PR China; Preventive health division, Xijing Hospital, Air Force Medical University (The Fourth Military Medical University), Xi'an 710032, PR China.
Int J Biol Macromol. 2024 Jun;270(Pt 2):132468. doi: 10.1016/j.ijbiomac.2024.132468. Epub 2024 May 17.
The current outbreak of mpox presents a significant threat to the global community. However, the lack of mpox-specific drugs necessitates the identification of additional candidates for clinical trials. In this study, a network medicine framework was used to investigate poxviruses-human interactions to identify potential drugs effective against the mpox virus (MPXV). The results indicated that poxviruses preferentially target hubs on the human interactome, and that these virally-targeted proteins (VTPs) tend to aggregate together within specific modules. Comorbidity analysis revealed that mpox is closely related to immune system diseases. Based on predicted drug-target interactions, 268 drugs were identified using the network proximity approach, among which 23 drugs displaying the least side-effects and significant proximity to MPXV were selected as the final candidates. Lastly, specific drugs were explored based on VTPs, differentially expressed proteins, and intermediate nodes, corresponding to different categories. These findings provide novel insights that can contribute to a deeper understanding of the pathogenesis of MPXV and development of ready-to-use treatment strategies based on drug repurposing.
当前的猴痘疫情对全球社会构成了重大威胁。然而，由于缺乏针对猴痘的特异性药物，有必要确定更多可用于临床试验的候选药物。在本研究中，我们使用网络医学框架来研究痘病毒与人类的相互作用，以确定对猴痘病毒（MPXV）有效的潜在药物。结果表明，痘病毒优先靶向人类相互作用组中的枢纽节点，并且这些病毒靶向蛋白（VTPs）倾向于在特定模块内聚集在一起。共病分析显示，猴痘与免疫系统疾病密切相关。基于预测的药物-靶点相互作用，使用网络接近度方法确定了268种药物，其中选择了23种副作用最小且与MPXV显著接近的药物作为最终候选药物。最后，基于VTPs、差异表达蛋白和中间节点，探索了对应不同类别的特异性药物。这些发现提供了新的见解，有助于更深入地了解MPXV的发病机制，并基于药物重新利用开发现成的治疗策略。
