Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs

J Med Virol. 2019 Nov;91(11):2016-2024. doi: 10.1002/jmv.25544. Epub 2019 Jul 25.


The development of therapies for human smallpox is needed due to the increasing concern over the potential use of smallpox virus as a biological weapon. Here, we report a high-throughput screening for anti-smallpox virus drugs from a 767-small-molecule library, employing two vaccinia virus (VACV) strains containing firefly luciferase (VTT-Fluc and VG9-Fluc) as surrogate viruses. Using an eight-point dose response format assay, 26 compounds of different pharmacological classes were identified with in vitro anti-VACV activities. Mycophenolate mofetil (MMF) and tranilast (TRA) were detected to possess the highest anti-VACV potency (selectivity index values of >334 and >74, respectively); they could inhibit VTT-Fluc replication in nude mice at 5 days post-infection by 99% (10 mg/kg, P < .01) and 59% (45 mg/kg, P = .01), respectively, as indicated by bioluminescent intensity. In conclusion, MMF and TRA are promising anti-smallpox virus candidates for further optimization and repurposing for use in clinical practice.

Keywords: approved drugs; inhibitor; screening; smallpox; vaccinia virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Chlorocebus aethiops
  • Drug Approval
  • Drug Discovery
  • Drug Repositioning*
  • Female
  • High-Throughput Screening Assays*
  • Mice
  • Mice, Nude
  • Small Molecule Libraries / pharmacology*
  • Smallpox / drug therapy
  • Vaccinia / drug therapy
  • Vaccinia virus / drug effects*
  • Vero Cells


  • Antiviral Agents
  • Small Molecule Libraries