Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options

Josset, Laurence; Zeng, Hui; Kelly, Sara M.; Tumpey, Terrence M.; Katze, Michael G.

Our in silico drug prediction was further validated by literature mining, revealing that out of the 26 drugs predicted to have an effect on at least one IAV in the present study, 17 have already been tested against influenza in cell or mouse models and 14 had antiviral effects in those tests (see Table S1 in the supplemental material). Among the 3 drugs that did not show any effect on influenza virus replication or pathogenicity, dexamethasone was predicted only to be a potential anti-H7N7 agent, since it had a positive z score for H7N9, H3N2, and H5N1 infections at early time points and could therefore increase early viral replication. This could be linked to the controversial role of corticosteroids in patients with influenza acute respiratory distress syndrome (ARDS), for which very early corticosteroid therapy may be harmful (35) . Most likely, several drugs predicted here that had previously known anti-IAV effects may have broad antiviral effects and could be active against H7N9. FDA-approved drugs that are already used in clinics for diverse indications but not influenza and that were identified in our in silico screening and with previously published antiinfluenza effects, such as chloroquine (36) , are particularly interesting to consider for therapeutic intervention against H7N9.