Ultrasmall Copper (I) Sulfide Nanoparticles Block Hepatitis B Virus.

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.