並列タイトル等トポイソメラーゼ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
授与機関名Nagasaki University (長崎大学)
一般注記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)
著作権情報© 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/).
関連情報http://hdl.handle.net/10069/00042264
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）