Further evidence that PN-SIA49 binds to an epitope on the HA stem region is given by lack of protease susceptibility of the HA at low pH in the presence of PN-SIA49. Exposure to low pH followed by trypsin digestion results in degradation of HA. In contrast, when the HA is pre-treated with PN-SIA49, most HA is retained in a protease resistant, pre-fusion form ( Figure 2 ).