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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Autores principales: Shufen Li, Meidi Ye, Yuanqiao Chen, Yulan Zhang, Jiachen Li, Wei Liu, Hao Li, Ke Peng
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Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/b4bca0db47a34599846359711783aedb
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic bunyavirus
SFTSV
SARS-CoV-2
anti-viral drug screening
toosendanin
Therapeutics. Pharmacology
RM1-950
spellingShingle 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
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