A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata
The protease Mpro (referred to as 3CLpro or 3CL protease) is a cysteine protease that is highly conserved in coronavirus and is indispensable for viral replication. Because there is no homologous protein for MPro in the human body, SARS-CoV-2 3CL protease is an ideal target against coronavirus. Blet...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Natural Products |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fntpr.2024.1372623/full |
| _version_ | 1797238481841291264 |
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| author | Yuyu Yang Fei Zhang Fei Zhang Shihan Liu Wenfang Jin Qianshan Shao Chunxiao Li Baolei Fan |
| author_facet | Yuyu Yang Fei Zhang Fei Zhang Shihan Liu Wenfang Jin Qianshan Shao Chunxiao Li Baolei Fan |
| author_sort | Yuyu Yang |
| collection | DOAJ |
| description | The protease Mpro (referred to as 3CLpro or 3CL protease) is a cysteine protease that is highly conserved in coronavirus and is indispensable for viral replication. Because there is no homologous protein for MPro in the human body, SARS-CoV-2 3CL protease is an ideal target against coronavirus. Bletilla striata (Reich. Bf.) is a well-known form of Traditional Chinese Medicine and can exert many pharmacological effects, including hemostasis, anti-microbial and anti-virus activities. Our preliminary screening showed that the n-butanol component of a methanol extract of B. striata exhibited potent inhibitory activity against SARS-CoV-2 3CL protease (58.82% at 200 μg/mL). In this study, we biologically evaluated ten isolated chemical compounds from B. striata and investigated the inhibitory activities of its constituents on SARS-CoV-2 3CL protease. Following bioactivity-guided fractionation, four bibenzyls (1, 4, 6 and 7), three phenols (5, 8 and 9), two anthraquinones (2 and 3) and one glucosyloxybenzyl 2-isobutylmalate (10) were isolated and evaluated for their ability to inhibit SARS-CoV-2 3CL protease by fluorescence resonance energy transfer (FRET) analysis. The binding mode between compounds and enzymes was investigated by molecular docking and Saturation Transfer Differences - nuclear magnetic resonance (STD-NMR). Moreover, Pleiobibenzynin B (7), Blestritin B, Gymconopin D (4), Physcion, 3′-O-methyl dioscin III (6), Gastrodin (8) and caffeic acid (5) all exhibited inhibitory activity against 3CL protease in vitro. The four bibenzyls (1, 4, 6 and 7) exhibited good inhibitory activity against SARS-CoV-2 3CL protease (7.37–39.86 μM). These findings identify potential new inhibitors against SARS-CoV-2 3CL protease, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs. |
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| id | doaj.art-a0611759c3184744871dd3726851c905 |
| institution | Directory Open Access Journal |
| issn | 2813-2602 |
| language | English |
| last_indexed | 2024-04-24T17:36:20Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Natural Products |
| spelling | doaj.art-a0611759c3184744871dd3726851c9052024-03-28T05:06:52ZengFrontiers Media S.A.Frontiers in Natural Products2813-26022024-03-01310.3389/fntpr.2024.13726231372623A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striataYuyu Yang0Fei Zhang1Fei Zhang2Shihan Liu3Wenfang Jin4Qianshan Shao5Chunxiao Li6Baolei Fan7Hubei University of Science and Technology, Xianning, ChinaHubei University of Science and Technology, Xianning, ChinaShenzhen University, Shenzhen, ChinaHubei University of Science and Technology, Xianning, ChinaHubei University of Science and Technology, Xianning, ChinaHubei University of Science and Technology, Xianning, ChinaHubei University of Science and Technology, Xianning, ChinaHubei University of Science and Technology, Xianning, ChinaThe protease Mpro (referred to as 3CLpro or 3CL protease) is a cysteine protease that is highly conserved in coronavirus and is indispensable for viral replication. Because there is no homologous protein for MPro in the human body, SARS-CoV-2 3CL protease is an ideal target against coronavirus. Bletilla striata (Reich. Bf.) is a well-known form of Traditional Chinese Medicine and can exert many pharmacological effects, including hemostasis, anti-microbial and anti-virus activities. Our preliminary screening showed that the n-butanol component of a methanol extract of B. striata exhibited potent inhibitory activity against SARS-CoV-2 3CL protease (58.82% at 200 μg/mL). In this study, we biologically evaluated ten isolated chemical compounds from B. striata and investigated the inhibitory activities of its constituents on SARS-CoV-2 3CL protease. Following bioactivity-guided fractionation, four bibenzyls (1, 4, 6 and 7), three phenols (5, 8 and 9), two anthraquinones (2 and 3) and one glucosyloxybenzyl 2-isobutylmalate (10) were isolated and evaluated for their ability to inhibit SARS-CoV-2 3CL protease by fluorescence resonance energy transfer (FRET) analysis. The binding mode between compounds and enzymes was investigated by molecular docking and Saturation Transfer Differences - nuclear magnetic resonance (STD-NMR). Moreover, Pleiobibenzynin B (7), Blestritin B, Gymconopin D (4), Physcion, 3′-O-methyl dioscin III (6), Gastrodin (8) and caffeic acid (5) all exhibited inhibitory activity against 3CL protease in vitro. The four bibenzyls (1, 4, 6 and 7) exhibited good inhibitory activity against SARS-CoV-2 3CL protease (7.37–39.86 μM). These findings identify potential new inhibitors against SARS-CoV-2 3CL protease, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.https://www.frontiersin.org/articles/10.3389/fntpr.2024.1372623/fullBletilla striataSARS-CoV-2 3CL proteaseFRETmolecular dockingSTD-NMR |
| spellingShingle | Yuyu Yang Fei Zhang Fei Zhang Shihan Liu Wenfang Jin Qianshan Shao Chunxiao Li Baolei Fan A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata Frontiers in Natural Products Bletilla striata SARS-CoV-2 3CL protease FRET molecular docking STD-NMR |
| title | A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata |
| title_full | A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata |
| title_fullStr | A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata |
| title_full_unstemmed | A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata |
| title_short | A study of the protease inhibitory activity component of SARS-CoV-2 3CL in Bletilla striata |
| title_sort | study of the protease inhibitory activity component of sars cov 2 3cl in bletilla striata |
| topic | Bletilla striata SARS-CoV-2 3CL protease FRET molecular docking STD-NMR |
| url | https://www.frontiersin.org/articles/10.3389/fntpr.2024.1372623/full |
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