Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase.
Varghese, J.N., Smith, P.W., Sollis, S.L., Blick, T.J., Sahasrabudhe, A., McKimm-Breschkin, J.L., Colman, P.M.(1998) Structure 6: 735-746
- PubMed: 9655825 
- DOI: https://doi.org/10.1016/s0969-2126(98)00075-6
- Primary Citation of Related Structures:  
2QWA, 2QWB, 2QWC, 2QWD, 2QWE, 2QWF, 2QWG, 2QWH, 2QWI, 2QWJ, 2QWK - PubMed Abstract: 
Inhibitors of the influenza virus neuraminidase have been shown to be effective antiviral agents in humans. Several studies have reported the selection of novel influenza strains when the virus is cultured with neuraminidase inhibitors in vitro. These resistant viruses have mutations either in the neuraminidase or in the viral haemagglutinin. Inhibitors in which the glycerol sidechain at position 6 of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) has been replaced by carboxamide-linked hydrophobic substituents have recently been reported and shown to select neuraminidase variants. This study seeks to clarify the structural and functional consequences of replacing the glycerol sidechain of the inhibitor with other chemical constituents.
Organizational Affiliation: 
Biomolecular Research Institute 343 Royal Parade, Parkville, 3052, Australia. jose.varghese@bioresi.com.au