Dasabuvir inhibits human norovirus infection in human intestinal enteroids

Abstract

Human noroviruses (HuNoVs) are acute viral gastroenteritis pathogens that affect all age groups, yet no approved vaccines and drugs to treat HuNoV infection are available. In this study, with a human intestinal enteroid (HIE) culture system where HuNoVs are able to replicate reproducibly, we screened an antiviral compound library to identify compound(s) showing anti-HuNoV activity. Dasabuvir, which has been developed as an anti-hepatitis C virus agent, was found to inhibit HuNoV infection in HIEs at micromolar concentrations. Dasabuvir also inhibited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human A rotavirus (RVA) infection in HIEs. To our knowledge, this is the first study to screen an antiviral compound library for HuNoV using HIEs and we successfully identified dasabuvir as a novel anti-HuNoV inhibitor that warrants further investigation.

Dasabuvir suppresses esophageal squamous cell carcinoma growth in vitro and in vivo through targeting ROCK1

“…As an anti-HCV drug, dasabuvir interacted with HCV NS5B palm domain to inhibit the encoding of RNA dependent RNA polymerase (RdRp) necessary for replication of HCV genome [33]. Besides, dasabuvir showed antiviral activities against a variety of flaviviruses in vitro [34], dasabuvir partially inhibited Middle East respiratory syndrome coronavirus (MERS-CoV) RdRp activity [35] and inhibited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human rotavirus A (RVA) and human norovirus (HuNoVs) infection [36]. However, the molecular target in eukaryocyte and related function has not been investigated.…”

Electrolyzed hypochlorous acid water exhibits potent disinfectant activity against various viruses through irreversible protein aggregation

“…Moreover, the jejunal human intestinal organoid (HIO) J2 line was provided by Baylor College of Medicine under a material transfer agreement. To maintain HIO, the cells were embedded in Matrigel and cultured as 3D HIO in IntestiCult Organoid Growth Medium (STEMCELL, Vancouver, Canada;Ettayebi et al, 2016;Hayashi et al, 2021). Lastly, HepG2-hNTCP-C4 cells were maintained as previously described (Fauzyah et al, 2021).…”

“…To conduct the HuNoV infection experiment using the HIO culture system, differentiated 2D HIO monolayers were prepared as described previously (Ettayebi et al, 2016;Hayashi et al, 2021). Subsequently, the 2D HIO monolayers in 96-well plates were inoculated with 100 μL of the above mixtures for 1 h. Next, the cells were washed twice with a complete medium without growth factors (−) and cultured in IntestiCult ODN in the presence of 500 μM GCDCA, which promotes GII.4 HuNoV infection (Murakami et al, 2020).…”

“…After 24 h post-infection, the cells and medium were harvested and subjected to RNA extraction using a Direct-zol-96 RNA Kit (Zymo Research, Irvine, CA, United States). Lastly, the extracted RNAs were subjected to reverse transcription-quantitative polymerase chain reaction to measure HuNoV GEs using TaqMan Fast Virus 1-Step Master Mix (Thermo Fisher Scientific) and GII-specific primer/probe sets (Kageyama et al, 2003;Hayashi et al, 2021).…”

Infant and Adult Human Intestinal Enteroids are Morphologically and Functionally Distinct

“…Once established, HIEs can be passaged long-term making them a very valuable laboratory tool (5,6). HIEs have been widely used to interrogate gut physiology (7)(8)(9)(10)(11)(12), host-pathogen interactions (13)(14)(15)(16)(17)(18)(19), drug activity (20,21), and cell-to-cell communication (22,23). Although HIEs do not completely reflect the complexity of the intestine in terms of the immune and stromal cells, the enteric nervous system, or the microbiome, these transformative cultures are expanding our understanding of the cellular composition, morphology, and functionality of the human intestinal epithelium.…”