To examine whether differentiated progenitor epithelial cells support influenza virus infection, epithelial colony cells were cultured in collagen I coated dishes for 5 days in epithelial cell differentiation medium. On day 5, cells were infected with SwIV and influenza viral nucleoprotein (NP) was detected at 24 h after infection by IFA using mouse anti influenza A NP (Millipore) as primary antibody and rhodamine-labelled goat anti-mouse (Molecular Probes) as secondary antibody. Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza. The first global pandemic of the 21st century was announced by the World Health Organization (WHO) in 2009 due to the worldwide spread of influenza A subtype H1N1 (H1N1/09) [1] . More than 214 countries have reported laboratory confirmed cases, and more than 18,449 deaths have been recorded [2] . Currently, the neuraminidase inhibitor TamifluH (oseltamivir) remains the primary drug prescribed to patients infected with H1N1/09 [3] . However, the emergence of drug resistant viral strains [4] and limited drug administration window [5] exemplifies the need for additional therapies.