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Norovirus: targets and tools in antiviral drug discovery.
Biochem Pharmacol. 2014 Sep 01; 91(1):1-11.BP

Abstract

The development of antiviral strategies to treat or prevent norovirus infections is a pressing matter. Noroviruses are the number 1 cause of acute gastroenteritis, of foodborne illness, of sporadic gastroenteritis in all age groups and of severe acute gastroenteritis in children less than 5 years old seeking medical assistance [USA/CDC]. In developing countries, noroviruses are linked to significant mortality (~200,000 children <5 years old). Noroviruses are a major culprit for the closure of hospital wards, and associated with increased hospitalization and mortality among the elderly. Transplant patients have significant risk of acquiring persistent norovirus gastroenteritis. Control and prevention strategies are limited to the use of disinfectants and hand sanitizers, whose efficacy is frequently insufficient. Hence, there is an ample need for antiviral treatment and prophylaxis of norovirus infections. The fact that only a handful of inhibitors of norovirus replication have been reported can largely be attributable to the hampering inability to cultivate human noroviruses in cell culture. The Norwalk replicon-bearing cells and the murine norovirus-infected cell lines are the available models to assess in vitro antiviral activity of compounds. Human noroviruses have been shown to replicate (to some extent) in mice, calves, gnotobiotic pigs, and chimpanzees. Infection of interferon-deficient mice with the murine norovirus results in virus-induced diarrhea. Here we review recent developments in understanding which norovirus proteins or host cell factors may serve as targets for inhibition of viral replication. Given the recent advances, significant progress in the search for antiviral strategies against norovirus infections is expected in the upcoming years.

Authors+Show Affiliations

Rega Institute for Medical Research, KU Leuven - University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.Rega Institute for Medical Research, KU Leuven - University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. Electronic address: johan.neyts@rega.kuleuven.be.Rega Institute for Medical Research, KU Leuven - University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

24893351

Citation

Rocha-Pereira, Joana, et al. "Norovirus: Targets and Tools in Antiviral Drug Discovery." Biochemical Pharmacology, vol. 91, no. 1, 2014, pp. 1-11.
Rocha-Pereira J, Neyts J, Jochmans D. Norovirus: targets and tools in antiviral drug discovery. Biochem Pharmacol. 2014;91(1):1-11.
Rocha-Pereira, J., Neyts, J., & Jochmans, D. (2014). Norovirus: targets and tools in antiviral drug discovery. Biochemical Pharmacology, 91(1), 1-11. https://doi.org/10.1016/j.bcp.2014.05.021
Rocha-Pereira J, Neyts J, Jochmans D. Norovirus: Targets and Tools in Antiviral Drug Discovery. Biochem Pharmacol. 2014 Sep 1;91(1):1-11. PubMed PMID: 24893351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Norovirus: targets and tools in antiviral drug discovery. AU - Rocha-Pereira,Joana, AU - Neyts,Johan, AU - Jochmans,Dirk, Y1 - 2014/06/02/ PY - 2014/04/05/received PY - 2014/05/23/revised PY - 2014/05/27/accepted PY - 2014/6/4/entrez PY - 2014/6/4/pubmed PY - 2014/10/7/medline KW - Antiviral drugs KW - Antiviral targets KW - Cell culture models KW - Norovirus KW - Small animal models SP - 1 EP - 11 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 91 IS - 1 N2 - The development of antiviral strategies to treat or prevent norovirus infections is a pressing matter. Noroviruses are the number 1 cause of acute gastroenteritis, of foodborne illness, of sporadic gastroenteritis in all age groups and of severe acute gastroenteritis in children less than 5 years old seeking medical assistance [USA/CDC]. In developing countries, noroviruses are linked to significant mortality (~200,000 children <5 years old). Noroviruses are a major culprit for the closure of hospital wards, and associated with increased hospitalization and mortality among the elderly. Transplant patients have significant risk of acquiring persistent norovirus gastroenteritis. Control and prevention strategies are limited to the use of disinfectants and hand sanitizers, whose efficacy is frequently insufficient. Hence, there is an ample need for antiviral treatment and prophylaxis of norovirus infections. The fact that only a handful of inhibitors of norovirus replication have been reported can largely be attributable to the hampering inability to cultivate human noroviruses in cell culture. The Norwalk replicon-bearing cells and the murine norovirus-infected cell lines are the available models to assess in vitro antiviral activity of compounds. Human noroviruses have been shown to replicate (to some extent) in mice, calves, gnotobiotic pigs, and chimpanzees. Infection of interferon-deficient mice with the murine norovirus results in virus-induced diarrhea. Here we review recent developments in understanding which norovirus proteins or host cell factors may serve as targets for inhibition of viral replication. Given the recent advances, significant progress in the search for antiviral strategies against norovirus infections is expected in the upcoming years. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/24893351/Norovirus:_targets_and_tools_in_antiviral_drug_discovery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(14)00313-X DB - PRIME DP - Unbound Medicine ER -