Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in D...Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.展开更多
利用三极射频 直流负偏压 等离子体增强化学气相沉积技术在45#钢表面制备了附着力较强的Si B N复合薄膜;采用X射线衍射仪和X射线光电子能谱仪分析了所制备的Si B N复合薄膜的组成和结构,通过划痕试验和球 盘摩擦磨损试验考察了薄膜与基...利用三极射频 直流负偏压 等离子体增强化学气相沉积技术在45#钢表面制备了附着力较强的Si B N复合薄膜;采用X射线衍射仪和X射线光电子能谱仪分析了所制备的Si B N复合薄膜的组成和结构,通过划痕试验和球 盘摩擦磨损试验考察了薄膜与基体的附着力及摩擦学性能.结果表明:通过合理地控制工艺参数,并对试样基体施加适当的直流负偏压,可以制得含六方氮化硼(h BN)和立方氮化硼(c BN)混合相的Si B N复合薄膜;而在Si B N复合薄膜表面引入沉积MoS2薄膜可以改善其摩擦学性能.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82130101)the Youth Innovation Promotion Association of CAS(Grant No.2021333).
文摘Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.
文摘利用三极射频 直流负偏压 等离子体增强化学气相沉积技术在45#钢表面制备了附着力较强的Si B N复合薄膜;采用X射线衍射仪和X射线光电子能谱仪分析了所制备的Si B N复合薄膜的组成和结构,通过划痕试验和球 盘摩擦磨损试验考察了薄膜与基体的附着力及摩擦学性能.结果表明:通过合理地控制工艺参数,并对试样基体施加适当的直流负偏压,可以制得含六方氮化硼(h BN)和立方氮化硼(c BN)混合相的Si B N复合薄膜;而在Si B N复合薄膜表面引入沉积MoS2薄膜可以改善其摩擦学性能.
