PMC:7499584 / 9054-11531
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7499584","sourcedb":"PMC","sourceid":"7499584","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7499584","text":"Safety\nCelgosivir has passed safety studies in humans (Sels et al. 1999; Rathore et al. 2011). N-butyl-deoxynojirimycin (Miglustat) has been approved for clinical use since 2002 for Gaucher’s disease (Cox et al. 2000; Lachmann 2003), after tests in 2000 to show its activity was to decrease substrate biosynthesis. This safety data suggests that both should be investigated repurposed off-label for COVID19 infectivity, since safety, PK and dosage has already been established. Also, long-term, 24-month studies of Miglustat have established safety and efficacy (Pastores et al. 2005), where COVID19 treatment may require very brief application. Chang et al. (2013b) and Pérez-García et al. (2017) reviewed and recommended the use of ER glycosylation inhibitors as potential targets for viral therapeutics. Main side effects were GI, manageable by diet and anti-propulsives. Duvoglustat, (1-deoxymannojirimycin) (Fuhrmann et al. 1984) amphomycin and related compounds should also be tested. Considering the seriousness of this pandemic, researchers with access to these and other glycosylation inhibitors should collaborate with virology labs that can test the infectivity cycle of SARS COV2.\nFollowing Okayama’s earlier work (1973), Schwartz et al. (1974) showed stimulation of synthesis of free chondroitin sulfate chains by ß-D-xylosides in cultured cells. Esko and Montgomery (1995), following Okayama’s and Schwartz’s earlier work, described xyloside “primers” of glycans that could be employed in tissue culture to prevent sugars from attaching to proteins, proteoglycans and glycolipids. They found ß-D-xylosides initiate glycosaminoglycan (GAG) synthesis by substituting for endogenous xylosylated core proteins. Xylosides will also prime oligosaccharides that resemble glycolipids. N-acetyl-α-D-galactosaminides initiate O-linked oligosaccharide synthesis found on mucins and other glycoproteins and can be used to disrupt O-glycosylation. Disaccharides, (e.g. peracetylated N-acetyllactosaminide), can act as primers. Competing with endogenous substrates, they interdict proteoglycan and glycoprotein glycosylation. Esko used acetylated xylose derivatives where PNP-Xyl treatment decreased heparan sulfate expression on the cell surface of Syndecan 4 cells and abrogated the HCV transmission in a concentration-dependent manner (Shieh et al. 1992; Fritz et al. 1994; Fritz and Esko 2001). Xylosides and thioxylosides should be tested in SARS COV2 infectivity studies.","divisions":[{"label":"title","span":{"begin":0,"end":6}},{"label":"p","span":{"begin":7,"end":1192}}],"tracks":[{"project":"2_test","denotations":[{"id":"32829416-11249557-45163171","span":{"begin":67,"end":71},"obj":"11249557"},{"id":"32829416-22020302-45163172","span":{"begin":88,"end":92},"obj":"22020302"},{"id":"32829416-10801168-45163173","span":{"begin":212,"end":216},"obj":"10801168"},{"id":"32829416-16199246-45163174","span":{"begin":579,"end":583},"obj":"16199246"},{"id":"32829416-27526926-45163176","span":{"begin":692,"end":696},"obj":"27526926"},{"id":"32829416-6230538-45163177","span":{"begin":929,"end":933},"obj":"6230538"},{"id":"32829416-4372604-45163178","span":{"begin":1251,"end":1255},"obj":"4372604"},{"id":"32829416-1310996-45163179","span":{"begin":2352,"end":2356},"obj":"1310996"},{"id":"32829416-8276811-45163180","span":{"begin":2371,"end":2375},"obj":"8276811"},{"id":"T18259","span":{"begin":67,"end":71},"obj":"11249557"},{"id":"T61604","span":{"begin":88,"end":92},"obj":"22020302"},{"id":"T75643","span":{"begin":212,"end":216},"obj":"10801168"},{"id":"T43487","span":{"begin":579,"end":583},"obj":"16199246"},{"id":"T11317","span":{"begin":692,"end":696},"obj":"27526926"},{"id":"T94065","span":{"begin":929,"end":933},"obj":"6230538"},{"id":"T74623","span":{"begin":1251,"end":1255},"obj":"4372604"},{"id":"T66993","span":{"begin":2352,"end":2356},"obj":"1310996"},{"id":"T27546","span":{"begin":2371,"end":2375},"obj":"8276811"}],"attributes":[{"subj":"32829416-11249557-45163171","pred":"source","obj":"2_test"},{"subj":"32829416-22020302-45163172","pred":"source","obj":"2_test"},{"subj":"32829416-10801168-45163173","pred":"source","obj":"2_test"},{"subj":"32829416-16199246-45163174","pred":"source","obj":"2_test"},{"subj":"32829416-27526926-45163176","pred":"source","obj":"2_test"},{"subj":"32829416-6230538-45163177","pred":"source","obj":"2_test"},{"subj":"32829416-4372604-45163178","pred":"source","obj":"2_test"},{"subj":"32829416-1310996-45163179","pred":"source","obj":"2_test"},{"subj":"32829416-8276811-45163180","pred":"source","obj":"2_test"},{"subj":"T18259","pred":"source","obj":"2_test"},{"subj":"T61604","pred":"source","obj":"2_test"},{"subj":"T75643","pred":"source","obj":"2_test"},{"subj":"T43487","pred":"source","obj":"2_test"},{"subj":"T11317","pred":"source","obj":"2_test"},{"subj":"T94065","pred":"source","obj":"2_test"},{"subj":"T74623","pred":"source","obj":"2_test"},{"subj":"T66993","pred":"source","obj":"2_test"},{"subj":"T27546","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ec9c93","default":true}]}]}}