We further tested whether siM2 could also inhibit the replication of a highly pathogenic H5N1 avian influenza virus. As shown in Fig. 5A , although numbers of plaques were similar in different MDCK cell lines, smaller size of plaques were only found in shM2-MDCK cells, suggesting that siM2 inhibited replication of H5N1 virus. The cell lines were also infected with different amounts of H5N1 virus and culture supernatants were collected at different time points to determine the virus titers by HA assay. The virus replication was significantly inhibited in shM2-MDCK cells at all time-points, but shNP-MDCK just offered a minor inhibition effect at early stage of the virus infection (Fig. 5B ). These results further confirmed that siM2 could provide a more potent protection than siNP against H5N1 infection.