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.

Transcriptome-based antiviral prediction. We have previously shown that drugs reversing the host response to IAV or coronavirus infection may inhibit viral replication (24, 25) . In an effort to identify such potential antivirals that target the cellular response to these IAVs, we used two independent and complementary methods. The first method is a literature-based prediction using the Ingenuity Knowledge Database that identifies molecules known to regulate DE genes in an opposite direction (z score Ͻ Ϫ2) from that with IAV infection (Fig. 4A) . For each IAV, potential antivirals were identified as upstream regulators having significant z scores on at least 2 time points and no positive z scores at any other time point. Only a few drugs were identified as potential anti-H7N7 therapies while 23 compounds were identified as potential regulators of the response to H3N2 IAV. Thirteen compounds were identified as negative regulators of the response to H7N9, including several kinases inhibitors (SB203580, U0126, SP600125, LY294002, genistein, SB202190, JAK inhibitor I and KN-32), immunosuppressive drugs (cyclosporine A, fontolizumab, infliximab, etanercept) and one antibiotic (minocycline). Other drugs that were predicted antivirals for H5N1 and H3N2, but with lower z score for H7N9, included chloroquine, aspirin and resveratrol.