Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication.
Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication.
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DOI：
10.1016/j.isci.2023.107602
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发表时间：
2023-09-15
期刊：
影响因子：
5.8
通讯作者：
Flaumenhaft, Robert
中科院分区：
文献类型：
--
作者：
Lin, Lin;Chen, Da-Yuan;Scartelli, Christina;Xie, Huanzhang;Merrill-Skoloff, Glenn;Yang, Moua;Sun, Lijun;Saeed, Mohsan;Flaumenhaft, Robert
基于其安全性和广泛可用性，植物类黄酮已被评估为β-冠状病毒复制的抑制剂和COVID-19的治疗药物。SARS-CoV-2主要蛋白酶（Mpro）已被认为是类黄酮的靶标。然而，迄今为止还没有对类黄酮抗SARS-CoV-2 Mpro的活性进行全面的体外测试。我们筛选了1，019种不同的黄酮类化合物，以确定它们抑制SARS-CoV-2 Mpro的能力。活性化合物之间存在多种构效关系，如富集没食子酰化的黄酮和双黄酮，包括芹菜素的多个双黄酮类似物。在基于细胞的SARS-CoV-2复制试验中，最有效的抑制剂是芹菜素和没食子酰化的松属素类似物，松属素7-O-（3“-没食子酰-4”，6“-（S）-六羟基二苯酰）-β-D-葡萄糖（PGHG）。分子动力学模拟预测，PGHG闭塞S1结合位点通过没食子酰基基团，并诱导Mpro的构象变化。这些研究将推进植物类黄酮的开发-包括广泛可用的天然产品-以靶向β-冠状病毒。通过对大量黄酮类化合物库的HTS分析，鉴定出SARS-CoV-2主要蛋白酶抑制剂，其中富含没食子酰化化合物和双黄酮类化合物。没食子酰化的松属素（PGHG）通过其没食子酰基封闭S1结合位点，PGHG和芹菜素是SARS-CoV-2复制的最有效抑制剂药理学;自然科学;化学;天然产物化学;生物科学;生物化学;细胞生物学
Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple structure-activity relationships were identified among active compounds such as enrichment of galloylated flavonoids and biflavones, including multiple biflavone analogs of apigenin. In a cell-based SARS-CoV-2 replication assay, the most potent inhibitors were apigenin and the galloylated pinocembrin analog, pinocembrin 7-O-(3''-galloyl-4'',6''-(S)-hexahydroxydiphenoyl)-beta-D-glucose (PGHG). Molecular dynamic simulations predicted that PGHG occludes the S1 binding site via a galloyl group and induces a conformational change in Mpro. These studies will advance the development of plant-based flavonoids—including widely available natural products—to target β-coronaviruses. HTS of a large flavonoid library identified SARS-CoV-2 main protease inhibitors Galloylated compounds and biflavones were enriched among active compounds The galloylated pinocembrin, PGHG, occluded the S1 binding site via its galloyl group PGHG and apigenin were the most potent inhibitors of SARS-CoV-2 replication Pharmacology; Natural sciences; Chemistry; Natural product chemistry; Biological sciences; Biochemistry; Cell biology
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DOI：
10.1016/j.bbrc.2022.04.086
发表时间：
2022-06-30
影响因子：
3.1
作者：
Feng, Jingwen;Li, Dongyang;Zhang, Jin;Yin, Xiushan;Li, Jian
通讯作者：
Li, Jian
影响因子：
4.9
作者：
通讯作者：
--
DOI：
10.1080/14756366.2019.1690480
发表时间：
2020-01-01
影响因子：
5.6
作者：
Jo, Seri;Kim, Suwon;Kim, Mi-Sun
通讯作者：
Kim, Mi-Sun
影响因子：
5.4
作者：
Chen DY;Khan N;Close BJ;Goel RK;Blum B;Tavares AH;Kenney D;Conway HL;Ewoldt JK;Chitalia VC;Crossland NA;Chen CS;Kotton DN;Baker SC;Fuchs SY;Connor JH;Douam F;Emili A;Saeed M
通讯作者：
Saeed M
影响因子：
--
作者：
Kuzikov M;Costanzi E;Reinshagen J;Esposito F;Vangeel L;Wolf M;Ellinger B;Claussen C;Geisslinger G;Corona A;Iaconis D;Talarico C;Manelfi C;Cannalire R;Rossetti G;Gossen J;Albani S;Musiani F;Herzog K;Ye Y;Giabbai B;Demitri N;Jochmans D;Jonghe S;Rymenants J;Summa V;Tramontano E;Beccari AR;Leyssen P;Storici P;Neyts J;Gribbon P;Zaliani A
通讯作者：
Zaliani A