Discovery of novel antiviral agents directed against the influenza A virus nucleoprotein using photo-cross-linked chemical arrays

The nucleoprotein (NP) of the influenza virus is expressed in the early stage of infection and plays important roles in numerous steps of viral replication NP is relatively well conserved compared with viral surface spike proteins This study experimentally demonstrates that NP is a novel target for the development of new antiviral drugs against the influenza virus First, artificial analogs of mycalamide A in a chemical array bound specifically with high affinity to NP Second, the compounds inhibited multiplication of the influenza virus Furthermore, surface plasmon resonance imaging experiments demonstrated that the binding activity of each compound to NP correlated with its antiviral activity Finally, it was shown that these compounds bound NP within the N-terminal 110-amino acid region but their binding abilities were dramatically reduced when the N-terminal 13-amino acid tail was deleted, suggesting that the compounds might bind to this region, which mediates the nuclear transport of NP and its binding to viral RNA These data suggest that compound binding to the N-terminal 13-amino acid tail region may inhibit viral replication by inhibiting the functions of NP Collectively, these results strongly suggest that chemical arrays are convenient tools for the screening of viral product inhibitors (C) 2010 Elsevier Inc All rights reserved