Sialidases viral

While many roles have been proposed quite early for viral sialidase (viral penetration into the host cell, provision of lower-molecular-weight metabolites for viral propagation, release of newly formed virus from the host cell, destruction of substances which protect the cell surface from virus binding, viral binding to the host cell surface by enzyme-substrate interaction), conflicting lines of evidence for each hypothesis have prevented the certain adoption of any of them. For details in an old and a new review, see those by Kelly (1963) and Drzeniek (1972). More recently Tsvetkova and Lipkind (1973) have suggested that the viral... 

Importantly, there was a general marked selectivity for inhibition of influenza A over influenza B viral sialidases in the carboxamide series (e.g. as seen with 27) (Smith et al. 1996, 1998), determined from crystallographic and molecular modelling studies (Smith et al. 1996 Taylor et al. 1998) to be due to the relative abilities of each of the sialidases to absorb the structural changes required to accommodate the hydrophobic alkyl chains in the glycerol side-chain binding pocket. In influenza... 

Strain Mutation Drug Level of sialidase activity and/or viral fitness... 

Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-V-acetyIneuraminic acid, Carbohydr Res 263 167-172 Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy, J Med Chem 13 697-704 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors, JAMA 297 1435-1442 Hay AJ (1992) The action of adamantanamines against influenza A viruses inhibition of the M2 ion channel protein, Semin Virol 3 21-30... 

Ryan DM, Ticehurst J, Dempsey M, Penn CR (1994) Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-iV-acetylneuraminic add) is consistent with extracellular actiivity of viral neuraminidase (sialidase), Antimicrob Agents Chemother 10 2270-2275... 

Fig. 3 Zanamivir , an antiviral drug which inhibits viral sialidases and below the mechanism of hydrolysis of sialosides with the transition state 4 mimed by Zanamivir .

Only a few bacterial and viral sialidases have been purified to high purity or even to protein homogeneity."0 Complete purification of sia-lidase on a preparative scale from the culture filtrate ofC. perfringens was achieved111 by using poly(acrylamide) gel-electrophoresis as the final purification step (see Section VI,1). It is necessary that such purified sialidases be available, as the presence of proteases or other gly-cosidases in the enzyme preparations would lead to severe errors, not only in studies of substrate specificity, but also in cell biological and medical studies (see Sections VI and VII). 

Purification of a variety of viral sialidases (influenza and paramyxovirus) after solubilization by proteases or detergents has been exten-... 

In no case is the amino acid composition of a sialidase yet known, and complete insight into the amino acids involved in enzyme catalysis is unavailable. There is one report demonstrating a possible involvement of tryptophan residues in enzyme catalysis.331 Establishing of the complete, amino acid sequence of sialidases from different sub-types of influenza virus is to be expected from the determination of the nucleotide sequence of the viral genome by using a plasmid technique.332 Preliminary results revealed the identity of the first 12 amino... 

Apart from the 4-O-acetylated sialic acids, another sialidase-resist-ant sialic acid exists in Nature, namely, the internal, Gal-bound, sialic acid residue of GM,. In contrast to this side-positioned sialic acid, the sialyl residues bound to the peripheral Gal of gangliosides, or to both the peripheral and the internal sialic acid residues forming oligo-sialvl chains in several members of the large ganglioside family,la can be readily removed by sialidases, as was tested with viral, bacterial, and mammalian enzymes.35 -35 1... 

Although viral sialidases seem to play a role, still poorly understood, in the mechanism of infection, and Neu2en5Ac derivatives inhibit virus replication in cell culture, no protective influence against influenza or parainfluenza virus infections in the intact host could be demonstrated by application of these inhibitors.400 This failure could be due to the rapid, urinary excretion of Neu2en5Ac observed after oral or intravenous application to rats and mice.401... 

IgG receptors on cultured, human lymphocytes.526 Sialidase treatment of lymphocytes from sensitized subjects increased the responsiveness to viral, bacterial, and fungal antigens.527 The same treatment of human, Herpes simplex virus-infected cells was found to enhance the sensitivity of the cells to lysis mediated by antibody and complement.528... 

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