Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

M Segment-Based Minigenome System of Severe Fever with Thrombocytopenia Syndrome Virus as a Tool for Antiviral Drug Screening

Hiroshi Yamada
,
Satoshi Taniguchi
ORCID logo ,
Masayuki Shimojima
,
Long Tan
,
Miyuki Kimura
,
Yoshitomo Morinaga
,
Takasuke Fukuhara
,
Yoshiharu Matsuura
,
Takashi Komeno
,
Yousuke Furuta
,
Masayuki Saijo
ORCID logo ,
Hideki Tani
* ORCID logo
Version 1 : Received: 14 April 2021 / Approved: 15 April 2021 / Online: 15 April 2021 (07:47:23 CEST)

A peer-reviewed article of this Preprint also exists.

Yamada, H.; Taniguchi, S.; Shimojima, M.; Tan, L.; Kimura, M.; Morinaga, Y.; Fukuhara, T.; Matsuura, Y.; Komeno, T.; Furuta, Y.; Saijo, M.; Tani, H. M Segment-Based Minigenome System of Severe Fever with Thrombocytopenia Syndrome Virus as a Tool for Antiviral Drug Screening. Viruses 2021, 13, 1061. Yamada, H.; Taniguchi, S.; Shimojima, M.; Tan, L.; Kimura, M.; Morinaga, Y.; Fukuhara, T.; Matsuura, Y.; Komeno, T.; Furuta, Y.; Saijo, M.; Tani, H. M Segment-Based Minigenome System of Severe Fever with Thrombocytopenia Syndrome Virus as a Tool for Antiviral Drug Screening. Viruses 2021, 13, 1061.

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case fatality rates of approximately 30%. There are few treatment options for SFTSV infection. SFTSV RNA synthesis is conducted using a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are, therefore, potential antiviral targets. A library of small molecule compounds was screened using a high-throughput screening (HTS) based on an SFTSV minigenome assay (MGA) in a 96-well microplate format to identify potential lead inhibitors of SFTSV RNA synthesis. The assay confirmed inhibitory activities of previously reported SFTSV inhibitors, favipiravir, and ribavirin. A small-scale screening using MGA identified four candidate inhibitors that inhibited SFTSV minigenome activity by more than 80% while exhibiting less than 20% cell cytotoxicity with selectivity index (SI) values of more than 100. These included mycophenolate mofetil, methotrexate, clofarabine, and bleomycin. Overall, these data demonstrate that the SFTSV MGA is useful for anti-SFTSV drug development research.

Keywords

SFTSV; minigenome assay; antivirals; antiviral screening; favipiravir; ribavirin

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.