Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2

Microbiol Immunol. 2020 Sep;64(9):635-639. doi: 10.1111/1348-0421.12828. Epub 2020 Jul 25.

Abstract

In this study, the anti-severe acute respiratory syndrome coronavirus-2 (anti-SARS-CoV-2) activity of mycophenolic acid (MPA) and IMD-0354 was analyzed. These compounds were chosen based on their antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. On SARS-CoV-2-infected VeroE6/TMPRSS2 monolayers, both MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only approximately 100-fold, its half maximal effective concentration was as low as 0.87 µ m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain-like protease and an in-depth study on its mechanism of action would be useful in the development of novel anti-SARS-CoV-2 drugs.

Keywords: IMD-0354; SARS-CoV-2; VeroE6/TMPRSS2; antiviral agents; mycophenolic acid.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Benzamides / pharmacology*
  • Betacoronavirus / drug effects*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Dengue Virus / drug effects
  • Humans
  • Mycophenolic Acid / pharmacology*
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Benzamides
  • N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
  • Mycophenolic Acid