Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.
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 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.
Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Kelvin K W
KKW
To
Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Ka-Yi
KY
Mok
Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Andy S F
ASF
Chan
Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Nam N
NN
Cheung
Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Pui
P
Wang
Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Yin-Ming
YM
Lui
State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Jasper F W
JFW
Chan
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, P. R. China.|Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Honglin
H
Chen
State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Kwok-Hung
KH
Chan
Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Richard Y T
RYT
Kao
Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, P. R. China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.|Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, P. R. China.
Kwok-Yung
KY
Yuen
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects* / Q000502:physiology; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D009173:Mycophenolic Acid / Q000494:pharmacology* / Q000633:toxicity; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009173:Mycophenolic Acid