Antiviral Activity of Olanexidine-Containing Hand Rub against Human Noroviruses

Ettayebi, Khalil; Salmen, Wilhelm; Imai, Kazutami; Hagi, Akifumi; Neill, Frederick H.; Atmar, Robert L.; Prasad, B. V. Venkataram; Estes, Mary K.

doi:10.1128/mbio.02848-21

Cited by 13 publications

(5 citation statements)

References 46 publications

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“…A breakthrough came when nontransformed human intestinal enteroids (HIEs) were proven to be a reproducible and biologically relevant system that supports the replication of multiple HuNoV strains 2,3 . HIEs have been successfully applied to (1) identify HuNoV strain-specific growth requirements 2,[4][5][6] , (2) identify neutralizing monoclonal antibodies and improve understanding of host responses to HuNoV for vaccine development [7][8][9][10] , and (3) monitor the environmental HuNoV load and the efficacy of disinfection strategies 11,12 . HIEs recapitulate the cellular complexity, diversity, and physiology of the human gastrointestinal tract along with host restriction and genetic factors and mimic strain-specific epidemiological host-virus infection patterns, making them an ideal system to dissect HuNoV infection and pathophysiology 13 .…”

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confidence: 99%

CLIC and membrane wound repair pathways enable pandemic norovirus entry and infection

et al. 2023

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Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell (S) domain interacts with both galectin-3 (gal-3) and apoptosis-linked gene 2-interacting protein X (ALIX), to orchestrate GII.4 cell entry. Recognition of the viral and cellular determinants regulating HuNoV entry provides insight into the infection process of a non-enveloped virus highlighting unique pathways and targets for developing effective therapeutics.

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CLIC and membrane wound repair pathways enable pandemic norovirus entry and infection

et al. 2023

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“…Human noroviruses (HuNoVs) cause nonbacterial acute gastroenteritis in patients of all ages and are highly contagious. 269 , 270 Intestinal organoids were cultured in monolayers infected with norovirus strains to monitor their replication and assess the virucidal efficacy of novel disinfectants. 269 , 271 , 272 In addition, human digestive organoids can also be used to identify norovirus inactivating factors.…”

Section: Microecosystem Research Using Digestive Organoidsmentioning

confidence: 99%

“… 269 , 270 Intestinal organoids were cultured in monolayers infected with norovirus strains to monitor their replication and assess the virucidal efficacy of novel disinfectants. 269 , 271 , 272 In addition, human digestive organoids can also be used to identify norovirus inactivating factors. 273 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease 2019 (COVID-19), has caused a global acute respiratory disease pandemic; as a highly contagious and pathogenic coronavirus, its emergence seriously threatens human health and public safety.…”

Section: Microecosystem Research Using Digestive Organoidsmentioning

confidence: 99%

Applications of human organoids in the personalized treatment for digestive diseases

Wang

Guo

Jin

et al. 2022

Sig Transduct Target Ther

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Digestive system diseases arise primarily through the interplay of genetic and environmental influences; there is an urgent need in elucidating the pathogenic mechanisms of these diseases and deploy personalized treatments. Traditional and long-established model systems rarely reproduce either tissue complexity or human physiology faithfully; these shortcomings underscore the need for better models. Organoids represent a promising research model, helping us gain a more profound understanding of the digestive organs; this model can also be used to provide patients with precise and individualized treatment and to build rapid in vitro test models for drug screening or gene/cell therapy, linking basic research with clinical treatment. Over the past few decades, the use of organoids has led to an advanced understanding of the composition of each digestive organ and has facilitated disease modeling, chemotherapy dose prediction, CRISPR-Cas9 genetic intervention, high-throughput drug screening, and identification of SARS-CoV-2 targets, pathogenic infection. However, the existing organoids of the digestive system mainly include the epithelial system. In order to reveal the pathogenic mechanism of digestive diseases, it is necessary to establish a completer and more physiological organoid model. Combining organoids and advanced techniques to test individualized treatments of different formulations is a promising approach that requires further exploration. This review highlights the advancements in the field of organoid technology from the perspectives of disease modeling and personalized therapy.

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“…This development overcame a five-decade barrier in laboratory models for HuNoVs, opening new avenues for investigating HuNoV biology. Since the establishment of the HIE system, significant advancements have been made in unraveling various aspects of HuNoV biology, including strain-specific differences in replication, methods of virus inactivation, innate immune responses, antiviral susceptibility, and characterization of neutralizing antibodies (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Here, we report further advancements in the HIE culture system by testing HuNoV infection in multiple unique HIE lines and expanding the profile of cultivatable HuNoV strains.…”

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Insights into Human Norovirus Cultivation in Human Intestinal Enteroids

Ettayebi,

Kaur,

Patil

et al. 2024

Preprint

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Human noroviruses (HuNoVs) are a significant cause of both epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system for HuNoVs was a major obstacle in studying virus replication and pathogenesis for almost a half- century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We previously optimized culture media conditions and generated genetically-modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present additional advancements to this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity was evaluated and compared in new HIE models, including HIEs generated from different intestinal segments of individual adult organ donors, HIEs made from human embryonic stem cell-derived human intestinal organoids that were transplanted into mice (H9tHIEs), genetically-engineered (J4FUT2 knock-in [KI], J2STAT1 knock-out [KO]) HIEs, as well as HIEs derived from a patient with common variable immunodeficiency (CVID) and from infants. Our findings reveal that small intestinal HIEs, but not colonoids, from adults, H9tHIEs, HIEs from a CVID patient, and HIEs from infants support HuNoV replication with segment and strain-specific differences in viral infection. J4FUT2-KI HIEs exhibit the highest susceptibility to HuNoV infection, allowing the cultivation of a broader range of GI and GII HuNoV strains than previously reported. Overall, these results contribute to a deeper understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research.

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Antiviral Activity of Olanexidine-Containing Hand Rub against Human Noroviruses

Abstract: Human noroviruses (HuNoVs) are highly contagious and cause nonbacterial acute gastroenteritis in all age groups worldwide. Since the introduction of rotavirus vaccines, HuNoVs have become the leading cause of diarrheal illness in children.

Cited by 13 publications

References 46 publications

CLIC and membrane wound repair pathways enable pandemic norovirus entry and infection

CLIC and membrane wound repair pathways enable pandemic norovirus entry and infection

Applications of human organoids in the personalized treatment for digestive diseases

Insights into Human Norovirus Cultivation in Human Intestinal Enteroids

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