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Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus

A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx...

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Autores principales: Ma, Yaojia, Nakamoto, Shingo, Ao, Junjie, Qiang, Na, Kogure, Tadayoshi, Ogawa, Keita, Nakagawa, Miyuki, Fujiwara, Kisako, Iwanaga, Terunao, Kojima, Ryuta, Kanzaki, Hiroaki, Koroki, Keisuke, Kobayashi, Kazufumi, Kanogawa, Naoya, Kiyono, Soichiro, Nakamura, Masato, Kondo, Takayuki, Nakagawa, Ryo, Ogasawara, Sadahisa, Muroyama, Ryosuke, Chiba, Tetsuhiro, Kato, Jun, Kato, Naoya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569680/
https://www.ncbi.nlm.nih.gov/pubmed/36233317
http://dx.doi.org/10.3390/ijms231912015
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author Ma, Yaojia
Nakamoto, Shingo
Ao, Junjie
Qiang, Na
Kogure, Tadayoshi
Ogawa, Keita
Nakagawa, Miyuki
Fujiwara, Kisako
Iwanaga, Terunao
Kojima, Ryuta
Kanzaki, Hiroaki
Koroki, Keisuke
Kobayashi, Kazufumi
Kanogawa, Naoya
Kiyono, Soichiro
Nakamura, Masato
Kondo, Takayuki
Nakagawa, Ryo
Ogasawara, Sadahisa
Muroyama, Ryosuke
Chiba, Tetsuhiro
Kato, Jun
Kato, Naoya
author_facet Ma, Yaojia
Nakamoto, Shingo
Ao, Junjie
Qiang, Na
Kogure, Tadayoshi
Ogawa, Keita
Nakagawa, Miyuki
Fujiwara, Kisako
Iwanaga, Terunao
Kojima, Ryuta
Kanzaki, Hiroaki
Koroki, Keisuke
Kobayashi, Kazufumi
Kanogawa, Naoya
Kiyono, Soichiro
Nakamura, Masato
Kondo, Takayuki
Nakagawa, Ryo
Ogasawara, Sadahisa
Muroyama, Ryosuke
Chiba, Tetsuhiro
Kato, Jun
Kato, Naoya
author_sort Ma, Yaojia
collection PubMed
description A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity. Recombinant GST-tagged HBx protein was applied on an FDA-approved drug library chip including 1018 compounds to determine binding affinity by surface plasmon resonance imaging (SPRi) using a PlexArray HT system. GST protein alone was used for control experiments. Candidate compounds were tested for anti-HBV activity as well as cell viability using HepG2.2.15.7 cells and HBV-infected human hepatocytes. Of the 1018 compounds screened, 24 compounds showed binding to HBx protein. Of the top 6 compounds with high affinity to HBx protein, tranilast was found to inhibit HBV replication without affecting cell viability using HepG2.2.15.7 cells. Tranilast also inhibited HBV infection using cultured human hepatocytes. Tranilast reduced HB antigen level dose-dependently. Overall, theSPRi screening assay identified novel drug candidates targeting HBx protein. Tranilast and its related compounds warrant further investigation for the treatment of HBV infection.
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spelling pubmed-95696802022-10-17 Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus Ma, Yaojia Nakamoto, Shingo Ao, Junjie Qiang, Na Kogure, Tadayoshi Ogawa, Keita Nakagawa, Miyuki Fujiwara, Kisako Iwanaga, Terunao Kojima, Ryuta Kanzaki, Hiroaki Koroki, Keisuke Kobayashi, Kazufumi Kanogawa, Naoya Kiyono, Soichiro Nakamura, Masato Kondo, Takayuki Nakagawa, Ryo Ogasawara, Sadahisa Muroyama, Ryosuke Chiba, Tetsuhiro Kato, Jun Kato, Naoya Int J Mol Sci Article A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity. Recombinant GST-tagged HBx protein was applied on an FDA-approved drug library chip including 1018 compounds to determine binding affinity by surface plasmon resonance imaging (SPRi) using a PlexArray HT system. GST protein alone was used for control experiments. Candidate compounds were tested for anti-HBV activity as well as cell viability using HepG2.2.15.7 cells and HBV-infected human hepatocytes. Of the 1018 compounds screened, 24 compounds showed binding to HBx protein. Of the top 6 compounds with high affinity to HBx protein, tranilast was found to inhibit HBV replication without affecting cell viability using HepG2.2.15.7 cells. Tranilast also inhibited HBV infection using cultured human hepatocytes. Tranilast reduced HB antigen level dose-dependently. Overall, theSPRi screening assay identified novel drug candidates targeting HBx protein. Tranilast and its related compounds warrant further investigation for the treatment of HBV infection. MDPI 2022-10-10 /pmc/articles/PMC9569680/ /pubmed/36233317 http://dx.doi.org/10.3390/ijms231912015 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ma, Yaojia
Nakamoto, Shingo
Ao, Junjie
Qiang, Na
Kogure, Tadayoshi
Ogawa, Keita
Nakagawa, Miyuki
Fujiwara, Kisako
Iwanaga, Terunao
Kojima, Ryuta
Kanzaki, Hiroaki
Koroki, Keisuke
Kobayashi, Kazufumi
Kanogawa, Naoya
Kiyono, Soichiro
Nakamura, Masato
Kondo, Takayuki
Nakagawa, Ryo
Ogasawara, Sadahisa
Muroyama, Ryosuke
Chiba, Tetsuhiro
Kato, Jun
Kato, Naoya
Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus
title Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus
title_full Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus
title_fullStr Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus
title_full_unstemmed Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus
title_short Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus
title_sort antiviral compounds screening targeting hbx protein of the hepatitis b virus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569680/
https://www.ncbi.nlm.nih.gov/pubmed/36233317
http://dx.doi.org/10.3390/ijms231912015
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