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• W159418411 abstract "Herpes simplex virus (HSV) initiates invasion of human cells by binding to the cell surface heparan sulfate (HS) glycosaminoglycan chains. This step is mediated by the viral envelope glycoproteins gC and/or gB. Sulfated polysaccharides are compounds that mimic the structure of HS chains, and therefore are capable of inhibiting HSV attachment to and subsequent infection of cells. However the high molecular weight and associated with it poor tissuepenetrating activity have limited potential antiviral application of sulfated polysaccharides in humans. Here we found that the HS mimetic PI-88, a sulfomannan oligosaccharide of low molecular weight, efficiently reduced, in contrast to conventional sulfated polysaccharides, the cell-to-cell spread of HSV. Analogues of PI-88 with chemical modifications based on the introduction of specific hydrophobic/aromatic group(s) at the reducing end of PI-88 oligosaccharide chain showed enhanced capability to inhibit infection of cells and the cell-tocell transmission of HSV and respiratory syncytial virus (RSV). One of these analogues (denoted 536), prepared by modification of PI-88 with cholestanol group, exhibited in contrast to the parental compound an HSV-inactivating activity. Furthermore, several disulfated cyclitols, identified by screening for an anti-HSV activity of a large number of low molecular weight sulfated compounds, efficiently reduced the cell-to-cell spread of HSV and demonstrated an HSV-inactivating activity. The second aim of this thesis was to elucidate the molecular basis for viral resistance to PI88. Variants of HSV type 1 (HSV-1) and type 2 (HSV-2), selected for by virus propagation in cultured cells in the presence of PI-88 were analysed. Many of these variants had a low infectious titer, indicative of a profound impairment in biological activities of the virus in response to continuous pressure from the drug. These variants were substantially resistant to PI-88 presence during their initial infection of cells and/or their cell-to-cell spread. Nucleotide sequence analysis revealed that PI-88 targeted predominantly the viral envelope glycoproteins that comprise mucin-like region(s), i.e., glycoprotein gC of HSV-1 and glycoprotein gG of HSV-2. The deletion of the mucin-like region of HSV-1 gC (amino acids 33-116) or the deletion of whole HSV-2 gG provided the virus with selective advantage to attach to and to infect cells in the presence of PI-88. In conclusion, we have identified several novel antiviral compounds. One of these compounds, the PI-88 analogue 536, seems to be an attractive candidate for the development of a topical virucide for prevention of genital HSV infections in humans. We have also identified a novel biological function of HSV-2 gG, i.e., its targeting by sulfated oligosaccharides, which suggests involvement of this protein in HSV-2 attachment to cells or in modulation of this step." @default.
• W159418411 created "2016-06-24" @default.
• W159418411 creator A5024992115 @default.
• W159418411 date "2007-06-20" @default.
• W159418411 modified "2023-09-27" @default.
• W159418411 title "Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols" @default.
• W159418411 cites W1482271921 @default.
• W159418411 cites W1509767963 @default.
• W159418411 cites W1510210255 @default.
• W159418411 cites W1516223106 @default.
• W159418411 cites W1533508293 @default.
• W159418411 cites W1552115305 @default.
• W159418411 cites W1564908571 @default.
• W159418411 cites W1570853101 @default.
• W159418411 cites W1577599165 @default.
• W159418411 cites W1579878633 @default.
• W159418411 cites W1604517259 @default.
• W159418411 cites W1643716094 @default.
• W159418411 cites W1695142101 @default.
• W159418411 cites W1778768141 @default.
• W159418411 cites W1793190047 @default.
• W159418411 cites W1798294004 @default.
• W159418411 cites W1855999912 @default.
• W159418411 cites W1867634595 @default.
• W159418411 cites W1882058356 @default.
• W159418411 cites W1884766802 @default.
• W159418411 cites W1915870046 @default.
• W159418411 cites W1927596245 @default.
• W159418411 cites W1963805168 @default.
• W159418411 cites W1964037828 @default.
• W159418411 cites W1964145161 @default.
• W159418411 cites W1964196863 @default.
• W159418411 cites W1964631389 @default.
• W159418411 cites W1970245110 @default.
• W159418411 cites W1971540677 @default.
• W159418411 cites W1972873370 @default.
• W159418411 cites W1975514230 @default.
• W159418411 cites W1975985087 @default.
• W159418411 cites W1976172519 @default.
• W159418411 cites W1976649122 @default.
• W159418411 cites W1980141034 @default.
• W159418411 cites W1980952944 @default.
• W159418411 cites W1981755056 @default.
• W159418411 cites W1986568660 @default.
• W159418411 cites W1991581875 @default.
• W159418411 cites W1992512657 @default.
• W159418411 cites W1992677585 @default.
• W159418411 cites W1992773224 @default.
• W159418411 cites W1995459626 @default.
• W159418411 cites W1997221411 @default.
• W159418411 cites W1997745179 @default.
• W159418411 cites W1999032534 @default.
• W159418411 cites W1999756472 @default.
• W159418411 cites W2001371234 @default.
• W159418411 cites W2011006965 @default.
• W159418411 cites W2015268137 @default.
• W159418411 cites W2020131358 @default.
• W159418411 cites W2020338189 @default.
• W159418411 cites W2023304225 @default.
• W159418411 cites W2024213191 @default.
• W159418411 cites W2024383984 @default.
• W159418411 cites W2024965784 @default.
• W159418411 cites W2025962934 @default.
• W159418411 cites W2027657241 @default.
• W159418411 cites W2029509365 @default.
• W159418411 cites W2031117917 @default.
• W159418411 cites W2032876500 @default.
• W159418411 cites W2033013765 @default.
• W159418411 cites W2034088795 @default.
• W159418411 cites W2036378300 @default.
• W159418411 cites W2039006290 @default.
• W159418411 cites W2040643579 @default.
• W159418411 cites W2043074722 @default.
• W159418411 cites W2045378555 @default.
• W159418411 cites W2046799663 @default.
• W159418411 cites W2047952679 @default.
• W159418411 cites W2054578983 @default.
• W159418411 cites W2065463433 @default.
• W159418411 cites W2068773381 @default.
• W159418411 cites W2071171181 @default.
• W159418411 cites W2071803370 @default.
• W159418411 cites W2074747538 @default.
• W159418411 cites W2077753375 @default.
• W159418411 cites W2080807893 @default.
• W159418411 cites W2083016901 @default.
• W159418411 cites W2083217959 @default.
• W159418411 cites W2085390874 @default.
• W159418411 cites W2086769942 @default.
• W159418411 cites W2091293864 @default.
• W159418411 cites W2092019188 @default.
• W159418411 cites W2095299808 @default.
• W159418411 cites W2096039378 @default.
• W159418411 cites W2103738194 @default.
• W159418411 cites W2105830107 @default.
• W159418411 cites W2113394330 @default.
• W159418411 cites W2123193533 @default.
• W159418411 cites W2124222169 @default.
• W159418411 cites W2124432186 @default.
• W159418411 cites W2126267287 @default.
• W159418411 cites W2126325884 @default.

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