Natural iminosugar derivatives of 1-deoxynojirimycin inhibit glycosylation of hepatitis viral envelope proteins.
A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans.
Jacob
James R
JR
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, NY 14853, USA.
Mansfield
Keith
K
You
Jung Eun
JE
Tennant
Bud C
BC
Kim
Young Ho
YH
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D012831:Bombyx / Q000737:chemistry*; D002144:Callithrix; D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology*; D018067:Flaviviridae / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification; D006031:Glycosylation; D006518:Hepatitis Viruses / Q000145:classification / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology; D007098:Imino Acids / Q000494:pharmacology*; D014020:Tissue Extracts / Q000302:isolation & purification* / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000187:drug effects / Q000378:metabolism*
D000998:Antiviral Agents; D002241:Carbohydrates; D007098:Imino Acids; D014020:Tissue Extracts; D014759:Viral Envelope Proteins; D017485:1-Deoxynojirimycin