Detail of "130525-62-1"

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Influenza virus variants with decreased sensitivity to 4-amino- and 4-guanidino-Neu5Ac2en

Influenza virus variants with decreased sensitivity to 4-amino- and 4-guanidino-Neu5Ac2en. Mckimm-Breschkin, J. L.; Blick, T.Several substances are used for example 130525-62-1 and 139110-80-8 which are their cas registry numbers. J.; Sahasrabudhe, A.; Varghese, J. N.; Bethell, R. C.; Hart, G. J.; Penn, C. R.; Colman, P. M. (Biomolecular Research Institute, Parkville 3052, Australia). International Congress Series, 1123(Options for the Control of Influenza III), 726-734 (English) 1996 Elsevier. CODEN: EXMDA4. ISSN: 0531-5131. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) An important aspect in the development of antiviral compds. is whether resistant variants emerge after continued exposure to the inhibitor. After several passages in each of two compds. 4-guanidino-Neu5Ac2en and 4-amino-Neu5Ac2en, which are specific inhibitors of the influenza neuraminidase (NA), NWS/G70C variants were isolated with decreased sensitivity to the inhibitors. Viruses were phenotyped in an enzyme inhibition assay, by sensitivity in both plaque and liq. culture assay, and by their ability to elute from agglutinated red blood cells in the presence of inhibitor. The predominant phenotype was cross-resistant to both compds. in cell culture and elution assays. Changes in these mutants mapped to the hemagglutinin (HA) gene. Mutations in the HA gene appear to alter the affinity of the HA for its receptor, thus reducing the dependence of the virus on NA activity for release from infected cells. A single NA mutant was selected, with a change in the conserved residue, Glu 119 to Gly, in the active site of the NA. Enzymic and crystallog. anal. confirmed that the Glu 119 to Gly mutation altered binding of the inhibitor. Mutations in either the HA or NA genes can thus lead to a decreased sensitivity to the NA inhibitors 4-amino-Neu5Ac2en and 4-guanidino-Neu5Ac2en. .