alpha-Galactosylceramide and novel synthetic glycolipids directly induce the innate host defense pathway and have direct activity against hepatitis B and C viruses.
alpha-Galactosylceramide is a glycolipid derived from marine sponges that is currently in human clinical trials as an anticancer agent. It has also been shown to be effective in reducing the amount of hepatitis B virus (HBV) DNA detected in mice that produce HBV constitutively from a transgene. It was assumed that all of the antiviral and antitumor activities associated with alpha-galactosylceramide were mediated through the activation of NK T cells. However, we report here an additional unpredicted activity of alpha-galactosylceramide as a direct antiviral agent and inducer of the innate host defense pathway. To exploit this activity, we have developed a new class of smaller, orally available glycolipids that also induce the innate host defense pathway and have direct activity against HBV and hepatitis C virus.
Mehta
Anand S
AS
Department of Biochemistry, The Jefferson Center, Jefferson Medical College, 700 E. Butler Ave., Doylestown, PA 18901, USA. anand.mehta@jefferson.edu
Gu
Baohua
B
Conyers
Bertha
B
Ouzounov
Serguey
S
Wang
Lijuan
L
Moriarty
Robert M
RM
Dwek
Raymond A
RA
Block
Timothy M
TM
D000818:Animals; D000998:Antiviral Agents; D015153:Blotting, Western; D002240:Carbohydrate Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics; D005699:Galactosylceramides / Q000494:pharmacology* / Q000633:toxicity; D006017:Glycolipids / Q000494:pharmacology* / Q000633:toxicity; D016174:Hepacivirus / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016899:Interferon-beta / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D011161:Porifera / Q000737:chemistry; D014764:Viral Proteins / Q000187:drug effects
C487652:2-amino-1-galactopyranosyloxy-3,4-dihydroxyoctadecane; D000998:Antiviral Agents; D004279:DNA, Viral; D005699:Galactosylceramides; D006017:Glycolipids; D014764:Viral Proteins; D016899:Interferon-beta