Inhibitory effect of Ephedra herba on human norovirus infection in human intestinal organoids

Abstract

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases worldwide with public health concern, yet no antiviral therapies have been developed. In this study, we aimed to screen crude drugs, which are components of Japanese traditional medicine, Kampo to see their effects on HuNoV infection using a reproducible HuNoV cultivation system, stem-cell derived human intestinal organoids/enteroids (HIOs). Among the 23 crude drugs tested, Ephedra herba significantly inhibited HuNoV infection in HIOs. A time-of-drug addition experiment indicated that this crude drug likely targets post-entry step for the inhibition. To our knowledge, this is the first anti-HuNoV inhibitor screen targeting crude drugs, and Ephedra herba was identified as a novel inhibitor candidate that merits further study.

Insights into Human Norovirus Cultivation in Human Intestinal Enteroids

“…This comparison, not previously undertaken in other studies that used OGM or ODM media (28,(39)(40)(41)(42)(43), provides guidance for laboratories using commercial media for HuNoV studies. Further, an evaluation of newly established lines, derived from intestinal segments of different donors, highlights strain-, donor-and segment-specific differences within the GII genogroup of HuNoVs.…”

“…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.…”

Drug screening identified that handelin inhibits feline calicivirus infection by inhibiting HSP70 expression in vitro

“…Human norovirus (HuNoV) also belongs to the family Caliciviridae, but it cannot sufficiently replicate in a cell culture system. Although relevant organoid models have been developed for drug screening, developing relevant antiviral drugs remains difficult due to insufficient replication of HuNoV in a cell culture system [45,46]. FCV has been used as a surrogate model for the screening of effective drugs for HuNoVs in a previous study [10].…”