Topoisomerase II as a Novel Antiviral Target against Panarenaviral Diseases

Material type: 博士論文

Author: Afowowe, Tosin Oladipo

Publisher: MDPI

Publication date: 2023-03-20

Material Format: Digital

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Name of awarding university/degree: Nagasaki University (長崎大学),博士(医学)

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Note (General)：: Although many arenaviruses cause severe diseases with high fatality rates each year, treatment options are limited to off-label use of ribavirin, and ...

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Material Type: 博士論文
Title: Topoisomerase II as a Novel Antiviral Target against Panarenaviral Diseases
Author/Editor: Afowowe, Tosin Oladipo
Author Heading: Afowowe, Tosin Oladipo
Publication, Distribution, etc.: MDPI
Publication Date: 2023-03-20
Publication Date (W3CDTF): 2023-03-20
Alternative Title: トポイソメラーゼIIは汎アレナウイルス病に対する新規抗ウイルス薬の標的となり得る
Periodical title: Viruses
No. or year of volume/issue: 15 1
Volume: 15
Issue: 1
Pages: 105-
ISSN (Periodical Title): ISSN : 1999-4915
Degree grantor/type: Nagasaki University (長崎大学)
Date Granted: 2023-03-20
Dissertation Number: 甲医歯薬第1523号
Degree Type: 博士(医学)
Text Language Code: eng
Subject Heading: arenaviruses
minigenome
drug screening
topoisomerase II
panarenaviral replication inhibitors
Target Audience: 一般
Note (General): Although many arenaviruses cause severe diseases with high fatality rates each year, treatment options are limited to off-label use of ribavirin, and a Food and Drug Administration (FDA)-approved vaccine is not available. To identify novel therapeutic candidates against arenaviral diseases, an RNA polymerase I-driven minigenome (MG) expression system for Lassa virus (LASV) was developed and optimized for high-throughput screening (HTS). Using this system, we screened 2595 FDA-approved compounds for inhibitors of LASV genome replication and identified multiple compounds including pixantrone maleate, a topoisomerase II inhibitor, as hits. Other tested topoisomerase II inhibitors also suppressed LASV MG activity. These topoisomerase II inhibitors also inhibited Junin virus (JUNV) MG activity and effectively limited infection by the JUNV Candid #1 strain, and siRNA knockdown of both topoisomerases (IIα and IIβ) restricted JUNV replication. These results suggest that topoisomerases II regulate arenavirus replication and can serve as molecular targets for panarenaviral replication inhibitors.
長崎大学学位論文学位記番号:博(医歯薬)甲第1523号学位授与年月日:令和5年3月20日
Author: Tosin Oladipo Afowowe, Yasuteru Sakurai, Shuzo Urata, Vahid Rajabali Zadeh, Jiro Yasuda
Citation: Viruses, 15(1), art. no. 105; 2022
identifier:Nagasaki University (長崎大学), 博士(医学) (2023-03-20)
Source: fulltext
https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=28229&item_no=1&attribute_id=70&file_no=1
Access Restrictions: インターネット公開
Rights (production): © 2022 by the authors. 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/).
Related Material: http://hdl.handle.net/10069/00042264
Related Material (DOI): 10.3390/v15010105
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ