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Dasabuvir inhibits human norovirus infection in human intestinal enteroids

Tsuyoshi Hayashi, Kosuke Murakami, Junki Hirano, Yoshiki Fujii, Yoko Yamaoka, Hirofumi Ohashi, Koichi Watashi, Mary K. Estes, Masamichi Muramatsu
doi: https://doi.org/10.1101/2021.07.02.450857
Tsuyoshi Hayashi
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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  • For correspondence: hayashit@nih.go.jp muramatsu@nih.go.jp
Kosuke Murakami
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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Junki Hirano
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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Yoshiki Fujii
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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Yoko Yamaoka
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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Hirofumi Ohashi
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
2Department of Applied Biological Sciences, Tokyo University of Science, Chiba, Japan
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Koichi Watashi
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
2Department of Applied Biological Sciences, Tokyo University of Science, Chiba, Japan
3Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan
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Mary K. Estes
4Departments of Molecular Virology and Microbiology and of Medicine, Baylor College of Medicine, Houston, Texas, USA
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Masamichi Muramatsu
1Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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  • For correspondence: hayashit@nih.go.jp muramatsu@nih.go.jp
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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.

Competing Interest Statement

M.K.E. is named as an inventor on patents related to cloning and cultivation of the Norwalk virus genome and is a consultant to and received research funding from Takeda Vaccines, Inc..

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 03, 2021.
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Dasabuvir inhibits human norovirus infection in human intestinal enteroids
Tsuyoshi Hayashi, Kosuke Murakami, Junki Hirano, Yoshiki Fujii, Yoko Yamaoka, Hirofumi Ohashi, Koichi Watashi, Mary K. Estes, Masamichi Muramatsu
bioRxiv 2021.07.02.450857; doi: https://doi.org/10.1101/2021.07.02.450857
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Dasabuvir inhibits human norovirus infection in human intestinal enteroids
Tsuyoshi Hayashi, Kosuke Murakami, Junki Hirano, Yoshiki Fujii, Yoko Yamaoka, Hirofumi Ohashi, Koichi Watashi, Mary K. Estes, Masamichi Muramatsu
bioRxiv 2021.07.02.450857; doi: https://doi.org/10.1101/2021.07.02.450857

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