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

Tsuyoshi Hayashi; Kosuke Murakami; Hirokazu Ando; Sayuri Ueno; Sakura Kobayashi; Masamichi Muramatsu; Takashi Tanikawa; Masashi Kitamura

doi:10.1016/j.bbrc.2023.05.127

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

Biochem Biophys Res Commun. 2023 Sep 3:671:200-204. doi: 10.1016/j.bbrc.2023.05.127. Epub 2023 Jun 2.

Authors

Tsuyoshi Hayashi¹, Kosuke Murakami², Hirokazu Ando³, Sayuri Ueno⁴, Sakura Kobayashi⁵, Masamichi Muramatsu⁶, Takashi Tanikawa⁷, Masashi Kitamura⁸

Affiliations

¹ Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, 208-0011, Japan. Electronic address: hayashit@niid.go.jp.
² Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, 208-0011, Japan.
³ Laboratory of Pharmacognosy, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
⁴ Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, 208-0011, Japan; Laboratory of Virology, Department of Infection Control and Immunology, Graduate School of Infection Comtrol Sciences, Kitasato University, Japan.
⁵ Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, 208-0011, Japan; Laboratory of Nutrition, Graduate School of Veterinary Science, Azabu University, Japan.
⁶ Department of Virology II, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, 208-0011, Japan; Department of Infectious Disease, Institute of Biomedical Research and Innovation, Research Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
⁷ Laboratory of Nutri-Pharmacotherapeutics Management, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama, 350-0295, Japan. Electronic address: tanikawa@josai.ac.jp.
⁸ Laboratory of Pharmacognosy, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama, 350-0295, Japan. Electronic address: kitamura@josai.ac.jp.

PMID: 37302295
DOI: 10.1016/j.bbrc.2023.05.127

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 22 crude drugs tested, Ephedra herba significantly inhibited HuNoV infection in HIOs. A time-of-drug addition experiment suggested that this crude drug more preferentially targets post-entry step than 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.

Keywords: Crude drug; Ephedra herba; Human norovirus; Intestinal organoids; Kampo.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Caliciviridae Infections* / drug therapy
Ephedra*
Gastroenteritis* / drug therapy
Humans
Intestines
Organoids