Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughp...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:b4bca0db47a34599846359711783aedb2021-11-11T09:10:40ZScreening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-21663-981210.3389/fphar.2021.735223https://doaj.org/article/b4bca0db47a34599846359711783aedb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.735223/fullhttps://doaj.org/toc/1663-9812Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughput screening of a natural extracts library for compounds with activities against SFTSV infection. Three hit compounds, notoginsenoside Ft1, punicalin, and toosendanin were identified for displaying high anti-SFTSV efficacy, in which, toosendanin showed the highest inhibition potency. Mechanistic investigation indicated that toosendanin inhibited SFTSV infection at the step of virus internalization. The anti-viral effect of toosendanin against SFTSV was further verified in mouse infection models, and the treatment with toosendanin significantly reduced viral load and histopathological changes in vivo. The antiviral activity of toosendanin was further expanded to another bunyavirus and the emerging SARS-CoV-2. This study revealed a broad anti-viral effect of toosendanin and indicated its potential to be developed as an anti-viral drug for clinical use.Shufen LiMeidi YeMeidi YeYuanqiao ChenYuanqiao ChenYulan ZhangJiachen LiWei LiuHao LiKe PengKe PengFrontiers Media S.A.articlebunyavirusSFTSVSARS-CoV-2anti-viral drug screeningtoosendaninTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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bunyavirus SFTSV SARS-CoV-2 anti-viral drug screening toosendanin Therapeutics. Pharmacology RM1-950 |
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bunyavirus SFTSV SARS-CoV-2 anti-viral drug screening toosendanin Therapeutics. Pharmacology RM1-950 Shufen Li Meidi Ye Meidi Ye Yuanqiao Chen Yuanqiao Chen Yulan Zhang Jiachen Li Wei Liu Hao Li Ke Peng Ke Peng Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2 |
description |
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughput screening of a natural extracts library for compounds with activities against SFTSV infection. Three hit compounds, notoginsenoside Ft1, punicalin, and toosendanin were identified for displaying high anti-SFTSV efficacy, in which, toosendanin showed the highest inhibition potency. Mechanistic investigation indicated that toosendanin inhibited SFTSV infection at the step of virus internalization. The anti-viral effect of toosendanin against SFTSV was further verified in mouse infection models, and the treatment with toosendanin significantly reduced viral load and histopathological changes in vivo. The antiviral activity of toosendanin was further expanded to another bunyavirus and the emerging SARS-CoV-2. This study revealed a broad anti-viral effect of toosendanin and indicated its potential to be developed as an anti-viral drug for clinical use. |
format |
article |
author |
Shufen Li Meidi Ye Meidi Ye Yuanqiao Chen Yuanqiao Chen Yulan Zhang Jiachen Li Wei Liu Hao Li Ke Peng Ke Peng |
author_facet |
Shufen Li Meidi Ye Meidi Ye Yuanqiao Chen Yuanqiao Chen Yulan Zhang Jiachen Li Wei Liu Hao Li Ke Peng Ke Peng |
author_sort |
Shufen Li |
title |
Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2 |
title_short |
Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2 |
title_full |
Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2 |
title_fullStr |
Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2 |
title_full_unstemmed |
Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2 |
title_sort |
screening of a small molecule compound library identifies toosendanin as an inhibitor against bunyavirus and sars-cov-2 |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/b4bca0db47a34599846359711783aedb |
work_keys_str_mv |
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