Enterovirus D68 Infection in Human Primary Airway and Brain Organoids: No Additional Role for Heparan Sulfate Binding for Neurotropism

Sridhar, Adithya; Depla, Josse; Mulder, Lance; Karelehto, Eveliina; Brouwer, Lieke; Kruiswijk, Leonie; Sá, Renata Vieira de; Meijer, Adam; Evers, Melvin M.; Kuppeveld, Frank J. M. van; Wolthers, Katja C.

doi:10.1128/spectrum.01694-22

Cited by 17 publications

(9 citation statements)

References 51 publications

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“…With Cmax values reported as ng/mL the micromolar concentration of a drug can be calculated using the formula below (Liston and Davis, 2017). Viral infections on HIE and HAE were performed as described previously (García-Rodríguez et al, 2021; Karelehto et al, 2018; Sridhar et al, 2022). Briefly, viral stocks were diluted to 10 3.8 TCID50/50 μL on ODMh for HIE or PneumaCult™-ALI medium without heparin for HAE.…”

Section: Methodsmentioning

confidence: 99%

Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models

García-Rodríguez,

Moreni,

Capendale

et al. 2023

Preprint

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Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae,andFlaviviridae).To this end, we used relevant human models of the airway and intestinal epithelium and regionalised neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses.Graphical abstractHighlightsHalofuginone hydrobromide was identified as a possible broad-spectrum host targeting antiviral drug.Human organoid models offer a physiologically relevant and clinically translatable model for antiviral research.Halofuginone hydrobromide shows antiviral efficacy against SARS-CoV-2, but not against EV-A71, PeV-A1, IAV, RV-A16, HCMV or ZIKV in relevant organoid models.The efficacy of Halofuginone hydrobromide is concentration dependent as well as on proline content of the host receptor(s) or host factors for the specific virus in question.

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Section: Methodsmentioning

confidence: 99%

Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models

García-Rodríguez,

Moreni,

Capendale

et al. 2023

Preprint

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“…In addition, the use of brain organoids already provided important insights into viral effects on the CNS by other viruses, such as herpes simplex virus-1 (HSV-1), 150 Japanese encephalitis virus, 151 Chikungunya virus (CHIKV), 140 JC virus 152 and very recently also Enterovirus D68, 153 among others. 153 A comprehensive list of virology-related studies that used brain organoids was published by Depla and colleagues. 154 Given this wide usage of brain organoids in virus research, there are now even manuals for handling brain organoids during and after infection for subsequent analysis.…”

Section: Brain Organoids As Model System To Dissect Viral Neurotropis...mentioning

confidence: 99%

“…[147][148][149] This phenotype was interpreted as model for Zika virus-induced microcephaly of newborns after congenital infection and marked an important milestone in neurotropic virus research. In addition, the use of brain organoids already provided important insights into viral effects on the CNS by other viruses, such as herpes simplex virus-1 (HSV-1), 150 Japanese encephalitis virus, 151 Chikungunya virus (CHIKV), 140 JC virus 152 and very recently also Enterovirus D68, 153 among others. 153 A comprehensive list of virology-related studies that used brain organoids was published by Depla and colleagues.…”

Section: Brain Organoids As Model System To Dissect Viral Neurotropis...mentioning

confidence: 99%

Human brain organoids to explore SARS‐CoV‐2‐induced effects on the central nervous system

Ostermann

Schaal

2023

Reviews in Medical Virology

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Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 . In less than three years, an estimated 600 million infections with SARS-CoV-2 occurred worldwide, resulting in a pandemic with tremendous impact especially on economic and health sectors. Initially considered a respiratory disease, COVID-19, along with its longterm sequelae (long-COVID) rather is a systemic disease. Neurological symptoms like dementia or encephalopathy were reported early during the pandemic as concomitants of the acute phase and as characteristics of long-COVID. An excessive inflammatory immune response is hypothesized to play a major role in this context. However, direct infection of neural cells may also contribute to the neurological aspects of (long)-COVID-19. To mainly explore such direct effects of SARS-CoV-2 on the central nervous system, human brain organoids provide a useful platform. Infecting these three-dimensional tissue cultures allows the study of viral neurotropism as well as of virus-induced effects on single cells or even the complex cellular network within the organoid. In this review, we summarize the experimental studies that used SARS-CoV-2-infected human brain organoids to unravel the complex nature of (long)-COVID-19-related neurological manifestations.

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“…The laboratory has established 3-D models of the human RT (by using HAE and lung organoids) and GI tract (with human gut organoids), in order to study SARS-CoV-2, picornavirus and CMV infections. Infection of these models with enterovirus A71, enterovirus D68, 83,84 human parechovirus CNS disease and SARS-CoV-2, 85 was also discussed. Professor Pajkrt concluded the talk by summarising the different uses of these models and highlighting the importance of the gut–brain axis organ-on-a-chip (see www.gutvibrations.org and Figure 5).…”

Section: Session 4: ‘Disease In a Dish’ Modelsmentioning

confidence: 99%

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

Naik,

Vadloori,

Poosala

et al. 2023

Altern Lab Anim

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Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Alternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day.

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Enterovirus D68 Infection in Human Primary Airway and Brain Organoids: No Additional Role for Heparan Sulfate Binding for Neurotropism

Cited by 17 publications

References 51 publications

Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models

Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models

Human brain organoids to explore SARS‐CoV‐2‐induced effects on the central nervous system

Advances in Animal Models and Cutting-Edge Research in Alternatives: Proceedings of the Third International Conference on 3Rs Research and Progress, Vishakhapatnam, 2022

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