Pralatrexate effectively inhibits the replication of monkeypox virus in vitro and in vivo

Jianshu Li; Siyu Li; Chaode Gu; Shaowen Shi; Xiao Li; Zhendong Guo; Zongzheng Zhao; Miao He; Zhiwei Wu

doi:10.1016/j.antiviral.2025.106232

Pralatrexate effectively inhibits the replication of monkeypox virus in vitro and in vivo

Antiviral Res. 2025 Jul 11:106232. doi: 10.1016/j.antiviral.2025.106232. Online ahead of print.

Authors

Jianshu Li¹, Siyu Li¹, Chaode Gu², Shaowen Shi³, Xiao Li³, Zhendong Guo³, Zongzheng Zhao³, Miao He⁴, Zhiwei Wu⁵

Affiliations

¹ Center for Public Health Research Medical School of Nanjing University Nanjing, PR China.
² State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, PR China.
³ Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130118, PR China.
⁴ Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China.
⁵ Center for Public Health Research Medical School of Nanjing University Nanjing, PR China; Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China; State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, PR China.

PMID: 40651557
DOI: 10.1016/j.antiviral.2025.106232

Abstract

The monkeypox virus (MPXV), an orthopoxvirus, has caused a number of major outbreaks and emerged as a global public health threat. Although drugs have been approved for the treatment of mpox, the efficacy and side effects remain unknown, which calls for the development of safe and effective drugs. Pralatrexate (PDX) is a fourth-generation antifolate drug with inhibitory activity against a wide range of viruses. In this study, we demonstrated the antiviral activity of PDX against MPXV in vitro and in vivo. Our results showed that PDX potently inhibited the MPXV replication at very low drug concentrations in vitro, and could significantly inhibit MPXV activity in dormice. In conclusion, this study found that PDX is an effective antiviral drug against MPXV infection, showing potential as a novel therapy for MPXV infection.

Keywords: Antiviral; MPXV; Poxviruses; Pralatrexate.