Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans

• Published in: Journal of general virology 2016-08, Vol.97 (8), p.1807-1817
• Main Authors: To, Kelvin K W, Mok, Ka-Yi, Chan, Andy S F, Cheung, Nam N, Wang, Pui, Lui, Yin-Ming, Chan, Jasper F W, Chen, Honglin, Chan, Kwok-Hung, Kao, Richard Y T, Yuen, Kwok-Yung
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - pharmacology; Antiviral Agents - toxicity; Cell Survival - drug effects; Dogs; Influenza A virus - drug effects; Influenza A virus - physiology; Influenza B virus; Influenza B virus - drug effects; Influenza B virus - physiology; Inhibitory Concentration 50; Madin Darby Canine Kidney Cells; Mycophenolic Acid - pharmacology; Mycophenolic Acid - toxicity; Orthomyxoviridae; Viral Load; Virus Replication - drug effects
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/jgv.0.000512

Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50