Antiviral activity and metabolism of the castanospermine derivative MDL 28,574, in cells infected with herpes simplex virus type 2.
The 6-O-butanoyl derivative of castanospermine (MDL 28,574: BUCAST), an inhibitor of glycoprotein processing, blocked the growth of herpes simplex virus type-2 with the effect markedly enhanced by exposure of cells to the compound pre- as well as post-infection. The effectiveness of the derivative corresponded to an increased uptake with greatest accumulation after virus infection. Gas chromatography/mass spectrometry identified the predominant component in MDL 28,574 treated cells as castanospermine, an inhibitor of alpha-glucosidase 1. The effects of this compound on the synthesis of viral glycoprotein, gB, was determined with the increased molecular weight of the mannose-rich precursor evidence for the modulation of glycoprotein processing.
Ahmed
S P
SP
MRC Collaborative Centre, Mill Hill, London, UK.
Nash
R J
RJ
Bridges
C G
CG
Taylor
D L
DL
Kang
M S
MS
Porter
E A
EA
Tyms
A S
AS
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000096:biosynthesis; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D007212:Indolizines / Q000378:metabolism* / Q000494:pharmacology*; D014709:Vero Cells; D010948:Viral Plaque Assay; D054836:Indolizidines
D000998:Antiviral Agents; D002250:Carbon Radioisotopes; D005959:Glucosidases; D006023:Glycoproteins; D007212:Indolizines; C070715:celgosivir; D054836:Indolizidines; C037806:castanospermine