Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV-2 papain-like protease
文献类型：期刊论文
| 作者 | Zou, Zhihui4; Shan, Huizhuang3,4; Sun, Demeng2; Xia, Li4; Shi, Yulong1; Wan, Jiahui4; Zhou, Aiwu4; Wu, Yunzhao4; Xu, Hanzhang4; Lei, Hu4 |
| 刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
 |
| 出版日期 | 2022-08-01 |
| 卷号 | 54期号:8页码:1133-1139 |
| 关键词 | COVID-19 SARS-CoV-2 PLpro Parthenolide deISGylation |
| ISSN号 | 1672-9145 |
| DOI | 10.3724/abbs.2022092 |
| 通讯作者 | Xu, Zhijian(zjxu@simm.ac.cn) ; Wu, Yingli(wuyingli@shsmu.edu.cn) |
| 英文摘要 | The coronavirus papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15 (ISG15), which enable it to participate in virus replication and host innate immune pathways. Therefore, PLpro is considered an attractive antiviral drug target. Here, we show that parthenolide, a germacrane sesquiterpene lactone, has SARS-CoV-2 PLpro inhibitory activity. Parthenolide covalently binds to Cys-191 or Cys-194 of the PLpro protein, but not the Cys-111 at the PLpro catalytic site. Mutation of Cys-191 or Cys-194 reduces the activity of PLpro. Molecular docking studies show that parthenolide may also form hydrogen bonds with Lys-192, Thr-193, and Gln-231. Furthermore, parthenolide inhibits the deISGylation but not the deubiquitinating activity of PLpro in vitro. These results reveal that parthenolide inhibits PLpro activity by allosteric regulation. |
| 资助项目 | National Key Research and Development Program of China[2017YFA0505200] ; Science and Technology Committee of Shanghai[19ZR1428700] ; Science and Technology Committee of Shanghai[20ZR1430600] ; National Natural Science Foundation of China[82170145] ; National Natural Science Foundation of China[81700157] ; National Natural Science Foundation of China[81700475] ; Innovative research team of high-level local universities in Shanghai[SHSMU-ZDCX20211802] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000860491100010 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302631]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Zhijian; Wu, Yingli |
| 作者单位 | 1.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Tsinghua Univ, Dept Chem, Beijing Adv Innovat Ctr Struct Biol,Tsinghua Peki, Minist Educ,Key Lab Bioorgan Phosphorus Chem & Ch, Beijing 100084, Peoples R China 3.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Lab Med, Guangzhou 510000, Guangdong, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Med SJTU SM,Fac Basic Med,Shanghai Tongren Ho, Chinese Acad Med Sci,Chem Biol Div,Shanghai Univ, Chinese Minist Educ,Res Unit 2019RU043,Key Lab Ce, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zou, Zhihui,Shan, Huizhuang,Sun, Demeng,et al. Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV-2 papain-like protease[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2022,54(8):1133-1139. |
| APA | Zou, Zhihui.,Shan, Huizhuang.,Sun, Demeng.,Xia, Li.,Shi, Yulong.,...&Wu, Yingli.(2022).Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV-2 papain-like protease.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,54(8),1133-1139. |
| MLA | Zou, Zhihui,et al."Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV-2 papain-like protease".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 54.8(2022):1133-1139. |
入库方式： OAI收割
来源：上海药物研究所
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