Generation and characterization of an influenza virus neuraminidase variant with decreased sensitivity to the neuraminidase-specific inhibitor 4-guanidino-Neu5Ac2en.
TJ Blick, T Tiong, A Sahasrabudhe, JN Varghese, PM Colman, GJ Hart, RC Bethell, JL McKimm-Breschkin
Virology | Published : 1995
A variant of the influenza virus NWS/G70C has been generated which has decreased sensitivity in vitro to the neuraminidase-specific inhibitor, 4-guanidino-Neu5Ac2en. The virus is 1000-fold less sensitive to the 4-guanidino-Neu5Ac2en in a plaque assay, but only 10-fold less sensitive to 4-amino-Neu5Ac2en. In an enzyme inhibition assay 250-fold more drug was needed to achieve inhibition comparable to that observed with the parent virus. In contrast to the plaque assay, the virus was fully sensitive to 4-amino-Neu5Ac2en in the enzyme inhibition assay. Kinetic analysis of 4-guanidino-Neu5Ac2en binding demonstrated that the variant no longer exhibited the slow binding characteristic seen with the..View full abstract