tetano
Editor, Senior Moderator
J Gen Virol. 2016 Jun 2. doi: 10.1099/jgv.0.000512. [Epub ahead of print]
[h=1]Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.[/h] To KK[SUP]1[/SUP], Mok KY[SUP]2[/SUP], Chan AS[SUP]3[/SUP], Cheung NN[SUP]4[/SUP], Wang P[SUP]5[/SUP], Lui YM[SUP]6[/SUP], Chan JF[SUP]7[/SUP], Chen H[SUP]8[/SUP], Chan KH[SUP]9[/SUP], Kao RY[SUP]10[/SUP], Yuen KY[SUP]11[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 ?M. 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 hours 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 8 different clinical isolates of A(H1N1), A(H3N2) and 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.
PMID: 27259985 [PubMed - as supplied by publisher]
[h=1]Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans.[/h] To KK[SUP]1[/SUP], Mok KY[SUP]2[/SUP], Chan AS[SUP]3[/SUP], Cheung NN[SUP]4[/SUP], Wang P[SUP]5[/SUP], Lui YM[SUP]6[/SUP], Chan JF[SUP]7[/SUP], Chen H[SUP]8[/SUP], Chan KH[SUP]9[/SUP], Kao RY[SUP]10[/SUP], Yuen KY[SUP]11[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 ?M. 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 hours 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 8 different clinical isolates of A(H1N1), A(H3N2) and 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.
PMID: 27259985 [PubMed - as supplied by publisher]