Zhang Yaru, Ma Tingnan, Yuan Tao, Su Lingyu, Yu Dongke, Zhong Lei
Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.
College of Stomatology, Chongqing Medical University, Chongqing, China; Chongqing Research Center for Oral Diseases and Biomedical Science, Chongqing, China.
Bioorg Med Chem Lett. 2025 Dec 1;128:130330. doi: 10.1016/j.bmcl.2025.130330. Epub 2025 Jul 11.
Mpox, a viral illness caused by the monkeypox virus (MPXV), has gained global attention due to its outbreaks worldwide in recent years. MPXV infections pose significant public health threats with notable transmission risks, yet specific antiviral treatments remain limited. Current therapeutic approaches primarily rely on smallpox vaccines and a limited number of broad-spectrum antiviral agents, such as tecovirimat, lacking specific drugs against MPXV. Thus, it remains a significant clinical need to develop anti-MPXV agents for the prevention and control of mpox outbreaks. In this review, we summarized the characteristics of MPXV in terms of viral structure, genome, and replication while reporting the recent progress in the development of small molecule anti-MPXV agents. Additionally, we discussed major obstacles in anti-MPXV drug development, including insufficient understanding of virus biology, the lack of reliable disease models, and limited resources for conducting large-scale clinical evaluations, and provided insights and perspectives for anti-MPXV therapies, with the aims of accelerating the development of effective treatments and contributing to preparedness against emerging orthopoxvirus threats.
猴痘是一种由猴痘病毒（MPXV）引起的病毒性疾病，近年来在全球范围内爆发，受到了全球关注。MPXV感染带来了重大的公共卫生威胁，具有显著的传播风险，但特定的抗病毒治疗方法仍然有限。目前的治疗方法主要依赖天花疫苗和少数几种广谱抗病毒药物，如tecovirimat，缺乏针对MPXV的特异性药物。因此，开发抗MPXV药物以预防和控制猴痘疫情仍然是一项重大的临床需求。在本综述中，我们总结了MPXV在病毒结构、基因组和复制方面的特征，同时报告了小分子抗MPXV药物开发的最新进展。此外，我们讨论了抗MPXV药物开发中的主要障碍，包括对病毒生物学的了解不足、缺乏可靠的疾病模型以及进行大规模临床评估的资源有限，并为抗MPXV治疗提供了见解和展望，旨在加速有效治疗方法的开发，并为应对新兴正痘病毒威胁做好准备。
