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

• Published in: Microbiology and immunology Vol. 64; no. 9; p. 635
• Main Authors: Kato, Fumihiro, Matsuyama, Shutoku, Kawase, Miyuki, Hishiki, Takayuki, Katoh, Hiroshi, Takeda, Makoto
• Format: Journal Article
• Language: English
• Published: Australia 01.09.2020
• Subjects: Animals; Antiviral Agents - pharmacology; Benzamides - pharmacology; Betacoronavirus - drug effects; Chlorocebus aethiops; Coronavirus Infections - drug therapy; Coronavirus Infections - virology; COVID-19; 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; IMD-0354; SARS-CoV-2; VeroE6/TMPRSS2; antiviral agents; mycophenolic acid
• ISSN: 1348-0421
• DOI: 10.1111/1348-0421.12828

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.