1
jiangnan university, No 1800 Lihu Avenue, jiangnan university, 214122, wuxi, CHINA.
2
Jiangnan University, School of Food Science and Technology, lihu road 1800#, 214122, Wuxi, CHINA.
3
Jiangnan University, School of Food Science and Technology, CHINA.
PMID: 33837622 DOI: 10.1002/anie.202103717
Abstract
Hepatitis B virus (HBV) poses a severe threat to public health and social development. Here, we synthesized 4 ± 0.5 nm copper (I) sulfide (Cu 2 S) nanoparticles (NPs) with 46 mdeg chiroptical properties at 530 nm to selectively cleavage HBV core antigen (HBcAg) and effectively blocked HBV assembly and prevented HBV infection both in vitro and in vivo under light at 808 nm. Experimental analysis showed that the Cu 2 S NPs specific bound with the functional domain from phenylalanine 23 to leucine 30 (F 23 F 24 P 25 S 26 V 27 R 28 D 29 L 30 ) from HBcAg primary sequence and the cutting site was between amino acid residues F 24 and P 25 . The l -Cu 2 S NPs showed greater cleavage activity than the d -Cu 2 S NPs and it was associated to the higher affinity of l -Cu 2 S NPs with the functional domain above. Under excitation at 808 nm, the intracellular HBcAg concentration was reduced by 95%, and in HBV transgenic mice, the levels of HBV surface protein antigen (HBsAg) and HBV DNA were decreased by 93% and 86%, respectively. Together, these results reveal the potential nanomedicine for HBV control and provide fresh tools for viral infection.
乙型肝炎病毒(HBV)对公共卫生和社会发展构成了严重威胁。在这里,我们合成了4±0.5 nm硫化铜(Cu 2 S)纳米粒子(NPs),在530 nm具有46 mdeg的手性,可选择性切割HBV核心抗原(HBcAg),有效阻断HBV装配并防止HBV感染。体外和体内在808 nm的光下。实验分析表明,与HBcAg一级序列的苯丙氨酸23到亮氨酸30(F 23 F 24 P 25 S 26 V 27 R 28 D 29 L 30)的亮氨酸30(F 23 F 24 P 25 S 26 V 27 R 28 D 29 L 30)的功能域特异性结合的Cu 2 S NPs的切割位点位于氨基之间。酸残基F 24和P 25。 1-Cu 2 S NPs显示出比d -Cu 2 S NPs更大的切割活性,并且与1-Cu 2 S NPs与上面的功能域具有更高的亲和力有关。在808 nm激发下,细胞内HBcAg浓度降低了95%,在HBV转基因小鼠中,HBV表面蛋白抗原(HBsAg)和HBV DNA的水平分别降低了93%和86%。总之,这些结果揭示了用于控制HBV的潜在纳米药物,并为病毒感染提供了新的工具。