RdRP-IN-4 (compound 11q), an aryl benzoyl hydrazide analog, is an orally active influenza A virus RNA-dependent RNA polymerase (RdRp) inhibitor by interacting with the PB1 subunit. RdRP-IN-4 exhibits potent inhibitory activity against the avian H5N1 flu strain with an EC50 of 18 nM in MDCK cells. RdRP-IN-4 displays excellent potency against the the H1N1 (A/PR/8/34) Flu A strain and Flu B strain (B/Lee/1940) with EC50 values of 53 nM and 20 nM, respectively. RdRP-IN-4 significantly inhibits the expression level of viral nucleoprotein (NP) in a dose-dependent manner. RdRP-IN-4 exhibits significant antiviral activity in infected mice.
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