Novel imino sugar derivatives demonstrate potent antiviral activity against flavivirusesv

Jinhong Chang, Lijuan Wang, Dongling Ma, Xiaowang Qu, Haitao Guo, Xiaodong Xu, Peter M. Mason, Nigel Bourne, Robert Moriarty, Baohua Gu, Ju Tao Guo, Timothy M. Block

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Imino sugars, such as JV-butyl-deoxynojirimycin and iV-nonyl- deoxynojirimycin (NNDNJ), are glucose ana-logues that selectively inhibit cellular at-glucosidase I and II in the endoplasmic reticulum and exhibit antiviral activities against many types of enveloped viruses. Although these molecules have broad-spectrum antiviral activity, their development has been limited by a lack of efficacy and/or selectivity. We have previously reported that a DNJ derivative with a hydroxylated cyclohexyl side chain, called OSL-95II, has an antiviral efficacy similar to that of NNDNJ but significantly less toxicity. Building upon this observation, a family of imino sugar derivatives containing an oxygenated side chain and terminally restricted ring structures were synthesized and shown to have low cytotoxicity and superior antiviral activity against members of the Flaviviridae family, including bovine viral diarrhea virus, dengue virus (DENV), and West Nile virus. Of particular Interest is that several of these novel imino sugar derivatives, such as PBDNJ0801, PBDNJ0803, and PBDNJ0804, potently inhibit DENV infection in vitro, with 90% effective concentration values at submicromolar concentrations and selectivity indices greater than 800. Therefore, these compounds represent the best in their class and may offer realistic candidates for the development of antiviral therapeutics against human DENV infections.

Original languageEnglish (US)
Pages (from-to)1501-1508
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number4
DOIs
StatePublished - Apr 2009

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Imino Sugars
Antiviral Agents
Dengue Virus
Virus Diseases
Flaviviridae
Bovine Viral Diarrhea Viruses
West Nile virus
Endoplasmic Reticulum
Viruses
Glucose

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Novel imino sugar derivatives demonstrate potent antiviral activity against flavivirusesv. / Chang, Jinhong; Wang, Lijuan; Ma, Dongling; Qu, Xiaowang; Guo, Haitao; Xu, Xiaodong; Mason, Peter M.; Bourne, Nigel; Moriarty, Robert; Gu, Baohua; Guo, Ju Tao; Block, Timothy M.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 4, 04.2009, p. 1501-1508.

Research output: Contribution to journalArticle

Chang, J, Wang, L, Ma, D, Qu, X, Guo, H, Xu, X, Mason, PM, Bourne, N, Moriarty, R, Gu, B, Guo, JT & Block, TM 2009, 'Novel imino sugar derivatives demonstrate potent antiviral activity against flavivirusesv', Antimicrobial Agents and Chemotherapy, vol. 53, no. 4, pp. 1501-1508. https://doi.org/10.1128/AAC.01457-08
Chang, Jinhong ; Wang, Lijuan ; Ma, Dongling ; Qu, Xiaowang ; Guo, Haitao ; Xu, Xiaodong ; Mason, Peter M. ; Bourne, Nigel ; Moriarty, Robert ; Gu, Baohua ; Guo, Ju Tao ; Block, Timothy M. / Novel imino sugar derivatives demonstrate potent antiviral activity against flavivirusesv. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 4. pp. 1501-1508.
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