Version 1
: Received: 7 May 2024 / Approved: 7 May 2024 / Online: 7 May 2024 (08:56:32 CEST)
How to cite:
Liu, L.; Wang, H.; Liu, L.; Cheng, F.; Aisa, H. A.; Li, C.; Meng, S. Rupestonic Acid Derivative YZH-106 Promotes Lysosomal Degradation of HBV L- and M-HBsAg via Direct Interaction with PreS2 Domain. Preprints2024, 2024050371. https://doi.org/10.20944/preprints202405.0371.v1
Liu, L.; Wang, H.; Liu, L.; Cheng, F.; Aisa, H. A.; Li, C.; Meng, S. Rupestonic Acid Derivative YZH-106 Promotes Lysosomal Degradation of HBV L- and M-HBsAg via Direct Interaction with PreS2 Domain. Preprints 2024, 2024050371. https://doi.org/10.20944/preprints202405.0371.v1
Liu, L.; Wang, H.; Liu, L.; Cheng, F.; Aisa, H. A.; Li, C.; Meng, S. Rupestonic Acid Derivative YZH-106 Promotes Lysosomal Degradation of HBV L- and M-HBsAg via Direct Interaction with PreS2 Domain. Preprints2024, 2024050371. https://doi.org/10.20944/preprints202405.0371.v1
APA Style
Liu, L., Wang, H., Liu, L., Cheng, F., Aisa, H. A., Li, C., & Meng, S. (2024). Rupestonic Acid Derivative YZH-106 Promotes Lysosomal Degradation of HBV L- and M-HBsAg via Direct Interaction with PreS2 Domain. Preprints. https://doi.org/10.20944/preprints202405.0371.v1
Chicago/Turabian Style
Liu, L., Changfei Li and Songdong Meng. 2024 "Rupestonic Acid Derivative YZH-106 Promotes Lysosomal Degradation of HBV L- and M-HBsAg via Direct Interaction with PreS2 Domain" Preprints. https://doi.org/10.20944/preprints202405.0371.v1
Abstract
Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. Mechanistic study by Biacore and docking analysis revealed that YZH-106 bound directly to PreS2 domain of L- and M-HBsAg, thereby blocking their entry to the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provide basis for design of novel compound therapy to target HBsAg against HBV infection.
Keywords
YZH-106; HBV; HBsAg; degradation
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
