Identification of Theaflavin-3,3'-Digallate as a Novel Zika Virus Protease Inhibitor.
Identification of Theaflavin-3,3'-Digallate as a Novel Zika Virus Protease Inhibitor.
复制标题
茶黄素-3,3'-二二酸酯作为新型寨卡病毒蛋白酶抑制剂的鉴定。
DOI：
10.3389/fphar.2020.514313
复制
发表时间：
2020
影响因子：
5.6
通讯作者：
Cen S
中科院分区：
文献类型：
--
作者：
Cui X;Zhou R;Huang C;Zhang R;Wang J;Zhang Y;Ding J;Li X;Zhou J;Cen S
越来越多的证据表明，寨卡病毒（ZIKV）与小头畸形和格林-巴利综合征等神经系统疾病密切相关。目前没有针对ZIKV感染的有效疫苗和FDA批准的抑制剂。黄病毒异二聚体丝氨酸蛋白酶NS 2B-NS 3在ZIKV成熟和复制中起重要作用，因此成为抗ZIKV疗法中有希望的靶标。在此，我们开发了一种基于荧光的筛选测定来寻找靶向ZIKV NS 2B-NS 3蛋白酶（ZIKVpro）的抑制剂，并鉴定了茶黄素-3，3 '-二没食子酸酯（ZP 10），一种来源于红茶的天然活性化合物，作为体外有效的ZIKV蛋白酶抑制剂（IC 50 = 2.3 μM）。ZP 10对ZIKV复制表现出剂量依赖性抑制作用（EC 50 = 7.65 μM）。蛋白质印迹分析表明，ZP 10抑制感染ZIKV或表达最小自切割蛋白酶NS 2B-3蛋白酶的细胞中病毒多蛋白前体的切割加工，导致病毒生长的抑制。此外，ZP 10显示直接结合ZIKVpro，并且对接模型进一步揭示ZP 10与ZIKVpro的蛋白水解腔中的几个关键残基相互作用。该研究强调了ZP 10通过ZIKVpro抑制具有抗ZIKV效力，这表明其在抗ZIKV疗法中的潜在应用。
Mounting evidence indicates that Zika virus (ZIKV) is closely related to neurological disorders such as microcephaly and Guillain-Barré syndrome. There are currently no effective vaccines and FDA-approved inhibitors against ZIKV infection. The flaviviral heterodimeric serine protease NS2B-NS3 plays an essential role in ZIKV maturation and replication, thus becoming a promising target in anti-ZIKV therapy. Herein, we developed a fluorescence-based screening assay to search for inhibitors targeting the ZIKV NS2B-NS3 protease (ZIKVpro), and identified theaflavin-3,3’-digallate (ZP10), a natural active compound derived from black tea, as a potent ZIKV protease inhibitor in vitro (IC50 = 2.3 μM). ZP10 exhibited dose-dependent inhibitory effect on ZIKV replication (EC50 = 7.65 μM). Western blot analysis suggested that ZP10 inhibited the cleavage processing of viral polyprotein precursor in cells either infected with ZIKV or expressing minimal self-cleaving proteinase NS2B-3 protease, resulting in inhibition of virus growth. Moreover, ZP10 was showed to directly bind to ZIKVpro, and a docking model further revealed that ZP10 interacted with several critical residues at the proteolytic cavity of the ZIKVpro. This study highlights that ZP10 has anti-ZIKV potency through ZIKVpro inhibition, which indicates its potential application in anti-ZIKV therapy.
登录
查看更多内容
影响因子：
3.7
作者：
Roy A;Lim L;Srivastava S;Lu Y;Song J
通讯作者：
Song J
影响因子：
7.6
作者：
Kamiyama N;Soma R;Hidano S;Watanabe K;Umekita H;Fukuda C;Noguchi K;Gendo Y;Ozaki T;Sonoda A;Sachi N;Runtuwene LR;Miura Y;Matsubara E;Tajima S;Takasaki T;Eshita Y;Kobayashi T
通讯作者：
Kobayashi T
DOI：
10.1016/j.bbrc.2018.06.062
发表时间：
2018-09-05
影响因子：
3.1
作者：
Li, Yan;Loh, Ying Ru;Kang, CongBao
通讯作者：
Kang, CongBao
影响因子：
5.2
作者：
Gao Y;Rankin GO;Tu Y;Chen YC
通讯作者：
Chen YC
影响因子：
3.5
作者：
Gruba, Natalia;Martinez, Jose Ignacio Rodriguez;Pyrc, Krzysztof
通讯作者：
Pyrc, Krzysztof