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

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

  • Viruses. 2021 Jun 3;13(6):1061. doi: 10.3390/v13061061.
Hiroshi Yamada 1,  Satoshi Taniguchi 2,  Masayuki Shimojima 2,  Long Tan 1,  Miyuki Kimura 1,  Yoshitomo Morinaga 1,  Takasuke Fukuhara 3 4,  Yoshiharu Matsuura 3 5,  Takashi Komeno 6,  Yousuke Furuta 6,  Masayuki Saijo 2,  Hideki Tani 1 7
Affiliations

Affiliations

  • 1 Department of Microbiology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama 930-0194, Japan.
  • 2 Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • 3 Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
  • 4 Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Hokkaido 060-8638, Japan.
  • 5 Center for Infectious Diseases Education and Research (CiDER), Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
  • 6 FUJIFILM Toyama Chemical Co., Ltd., Toyama 930-8508, Japan.
  • 7 Department of Virology, Toyama Institute of Health, Toyama 939-0363, Japan.
PMID: 34205062 DOI: 10.3390/v13061061
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 processed 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; antiviral screening; antivirals; favipiravir; minigenome assay; ribavirin.

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