Viruses, Vol. 15, Pages 105: Topoisomerase II as a Novel Antiviral Target against Panarenaviral Diseases
Viruses, Vol. 15, Pages 105: Topoisomerase II as a Novel Antiviral Target against Panarenaviral Diseases
Viruses doi: 10.3390/v15010105
Authors:
Tosin Oladipo Afowowe
Yasuteru Sakurai
Shuzo Urata
Vahid Rajabali Zadeh
Jiro Yasuda
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.
Source: Viruses - Category: Virology Authors: Tosin Oladipo Afowowe Yasuteru Sakurai Shuzo Urata Vahid Rajabali Zadeh Jiro Yasuda Tags: Article Source Type: research