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

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.