Infection of zebrafish larvae with human norovirus and evaluation of the in vivo efficacy of small-molecule inhibitors

Dycke, Jana Van; Cuvry, Arno; Knickmann, Jan; Ny, Annelii; Rakers, Sebastian; Taube, Stefan; Witte, Peter de; Neyts, Johan; Rocha‐Pereira, Joana

doi:10.1038/s41596-021-00499-0

Cited by 33 publications

(21 citation statements)

References 32 publications

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“…In addition, an increase in expression of several immune genes was also observed [ 34 ]. The zebrafish model has also been utilized for high throughput anti-HuNoV drug screening [ 219 , 220 ]. Of interest, a transgenic zebrafish expressing green fluorescent protein under the influence of an IFN stimulated gene promoter has been developed, providing an in vivo tracking system for viral infections [ 221 ].…”

Section: In Vivo Tools To Study Human Enteric Rna Virusesmentioning

confidence: 99%

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Aggarwal

Hassan

Baldridge

2021

Viruses

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Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis. However, many aspects of enteric viral infections remain elusive, demanding further study. Here, we describe the different in vitro and in vivo tools available to explore different pathophysiological attributes of human enteric RNA viruses, highlighting their advantages and limitations depending upon the question being explored. In addition, we discuss key areas and opportunities that would benefit from further methodological progress.

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Section: In Vivo Tools To Study Human Enteric Rna Virusesmentioning

confidence: 99%

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Aggarwal

Hassan

Baldridge

2021

Viruses

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“…The use of cell models in in vitro tests allows for the quick and precise determination of the antiviral activity of various preparations [ 38 ]. All results of in vitro studies on the action of plant-derived active metabolites (e.g., endpoint titration technique (EPTT), virus-induced cytopathic effect inhibition (CPE), virus yield reduction assay, MTT assay, plaque reduction assay, virus deactivation assay, virus adsorption assay, virus attachment, and virus penetration assay [ 39 ]) must also be confirmed by in vivo testing [ 40 , 41 , 42 ], which, at the next stage, is a necessary step in the application for registration with government food and drug control agencies and in making the preparation available to food pharmaceutical industries [ 43 ].…”

Section: Methodology Of Research Regarding the Antiviral Activity Of Phytochemicalsmentioning

confidence: 99%

Antiviral Potential of Plants against Noroviruses

et al. 2021

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Human noroviruses, which belong to the enterovirus family, are one of the most common etiological agents of food-borne diseases. In recent years, intensive research has been carried out regarding the antiviral activity of plant metabolites that could be used for the preservation of fresh food, because they are safer for consumption when compared to synthetic chemicals. Plant preparations with proven antimicrobial activity differ in their chemical compositions, which significantly affects their biological activity. Our review aimed to present the results of research related to the characteristics, applicability, and mechanisms of the action of various plant-based preparations and metabolites against norovirus. New strategies to combat intestinal viruses are necessary, not only to ensure food safety and reduce infections in humans but also to lower the direct health costs associated with them.

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“…More recently, breakthroughs have been made in zebrafish larvae, B-cell, and human intestinal enteroid (HIE) culture systems to support HuNoV replication [107][108][109]. For example, a protocol has recently been developed to evaluate antiviral effect and toxicity of small molecules in HuNoVinfected zebrafish larvae [110]. Using this model, a novel peptidomimetic protease inhibitor, which is structurally related to rupintrivir, has been shown to exhibit potent inhibition of HuNoV [111].…”

Section: In Vivo Testing-lead Validationmentioning

confidence: 99%

Norovirus Protease Structure and Antivirals Development

Zhao

Song

et al. 2021

Viruses

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Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is an excellent target for developing small-molecule inhibitors. The current strategy for developing HuNoV protease inhibitors is by targeting the enzyme’s active site and designing inhibitors that bind to the substrate-binding pockets located near the active site. However, subtle differential conformational flexibility in response to the different substrates in the polyprotein and structural differences in the active site and substrate-binding pockets across different genogroups, hamper the development of effective broad-spectrum inhibitors. A comparative analysis of the available HuNoV protease structures may provide valuable insight for identifying novel strategies for the design and development of such inhibitors. The goal of this review is to provide such analysis together with an overview of the current status of the design and development of HuNoV protease inhibitors.

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Infection of zebrafish larvae with human norovirus and evaluation of the in vivo efficacy of small-molecule inhibitors

Cited by 33 publications

References 32 publications

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Antiviral Potential of Plants against Noroviruses

Norovirus Protease Structure and Antivirals Development

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