The invention discloses application of leflunomide, teriflunomide, brequinar and derivatives thereof to treatment of virus infection, especially RNA virus infection. RNA viruses include but are not limited to influenza viruses, respiratory syncytial viruses, hand, foot and mouth viruses (EV71), dengue viruses (type-2 dengue viruses), Zika viruses and Japanese encephalitis viruses. The medicines have broad-spectrum and excellent antiviral activity and have relatively low toxicity to normal cells.