Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection
文献类型：期刊论文
| 作者 | Yao, Xingang3; Guo, Songxin3; Wu, Wenyu4; Wang, Jinan5; Wu, Shengen3; He, Shijun3 ; Wan, Yihong3; Nandakumar, Kutty Selva3; Chen, Xiaoguang1; Sun, Ning2
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| 刊名 | JOURNAL OF PHARMACOLOGICAL SCIENCES
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| 出版日期 | 2018-12 |
| 卷号 | 138期号:4页码:247-256 |
| 关键词 | RdRp inhibitor Quinazolinone derivative DENV2 infection |
| ISSN号 | 1347-8613 |
| DOI | 10.1016/j.jphs.2018.06.012 |
| 文献子类 | Article |
| 英文摘要 | Dengue virus (DENV) annually infects 400 million people worldwide. Unfortunately, there is lack of widely protective vaccine or drugs against DENV. The viral RNA-dependent RNA polymerase (RdRp) of NS5 protein is highly conserved among different DENV subtypes, thus presenting itself as an attractive target for drug design. In the current research, SPRi was performed to screen compounds against DENV2 RdRp and 5(1H)-Quinazolinone, 2-(4-bromophenyl)-2,3,4,6,7,8-hexahydro-7,7-dimethyl-1,3-diphenyl (Q63) was successfully screened out with a KD of 0.9 mM. Then, ITC and molecular docking assay was performed to access the binding mechanism between Q63 and DENV2 RdRp. Meanwhile, Q63 also decreased the intermediate dsRNA production, which was the product of RdRp. Further the antiviral effects of Q63 were evaluated on mosquito C6/36 cells and mammalian BHK-21 cells. Q63 reduced CPE and cell toxicity effect after DENV2 infection on C6/36 and BHK-21 cells, with an EC50 of 2.08 mM. Time of addition assay revealed that Q63 affected the early genome RNA replication stage, including genome RNA replication. In addition, Q63 down-regulated STAT1 phosphorylation, ISG15 and ISG54 after DENV2 infection. In summary, Q63 was found to be a novel RdRp non-nucleoside inhibitor and a potential lead compound for coping with DENV infectious disease in the future. (c) 2018 The Authors. Production and hosting by Elsevier B. V. on behalf of Japanese Pharmacological Society. |
| WOS关键词 | STYLE-RELATED DISEASES ; HEPATITIS-C-VIRUS ; DIGESTIVE-SYSTEM ; NS5 PROTEIN ; DENGUE ; DOMAIN ; CELLS |
| 资助项目 | Natural Science Foundation of China[81603118] ; Natural Science Foundation of China[81700854] ; Medical Scientific Research Foundation of Guangdong Province[A2016119] ; Guangdong Provincial Application Technology Research and the Development Project[2016B020237005] ; Pearl River Nova Program of Guangzhou[201806010119] ; Natural Science Foundation of Guangdong Province[2017A030313717] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000453009900004 |
| 出版者 | JAPANESE PHARMACOLOGICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279477]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Yao, Xingang; Liu, Shuwen |
| 作者单位 | 1.Southern Med Univ, Sch Publ Hlth, Guangzhou 510515, Guangdong, Peoples R China; 2.Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 510700, Guangdong, Peoples R China 3.Southern Med Univ, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Guangdong Prov Key Lab New Drug Screening, State Key Lab Organ Failure Res,Sch Pharmaceut Sc, Guangzhou 510515, Guangdong, Peoples R China; 4.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yao, Xingang,Guo, Songxin,Wu, Wenyu,et al. Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection[J]. JOURNAL OF PHARMACOLOGICAL SCIENCES,2018,138(4):247-256. |
| APA | Yao, Xingang.,Guo, Songxin.,Wu, Wenyu.,Wang, Jinan.,Wu, Shengen.,...&Liu, Shuwen.(2018).Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection.JOURNAL OF PHARMACOLOGICAL SCIENCES,138(4),247-256. |
| MLA | Yao, Xingang,et al."Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection".JOURNAL OF PHARMACOLOGICAL SCIENCES 138.4(2018):247-256. |
入库方式： OAI收割
来源：上海药物研究所
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