NDLI: Structure-Based Discovery of N-Sulfonylpiperidine-3-Carboxamides as Novel Capsid Assembly Modulators for Potent Inhibition of HBV Replication

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Structure-Based Discovery of N-Sulfonylpiperidine-3-Carboxamides as Novel Capsid Assembly Modulators for Potent Inhibition of HBV Replication

Content Provider	MDPI
Author	Yang, Yang Yan, Yu Yin, Jiaxin Hu, Jie Cai, Xuefei Hu, Jieli Xia, Jie Wang, Kai Tang, Ni Huang, Luyi
Copyright Year	2022
Description	As a key element during HBV replication, a nucleocapsid is considered a promising target for the treatment of chronic hepatitis B. The present study aimed to identify small molecules as novel capsid assembly modulators with antiviral activity. Structure-based virtual screening of an integrated compound library led to the identification of several types of HBV inhibitors. Among these inhibitors, N-sulfonylpiperidine-3-carboxamides (SPCs) potently reduced the amount of secreted HBV DNA. Through structure–activity relationship studies, we identified an SPC derivative, namely, C-39, which exhibited the highest antiviral activity without causing cytotoxicity. Mechanism studies showed that C-39 dose-dependently inhibited the formation of HBV capsid, synthesis of cccDNA, e antigen (HBeAg), viral pregenomic RNA (pgRNA), and HBV DNA levels, thereby restraining HBV replication. In summary, SPCs represent a new class of capsid assembly modulators. Further optimization of SPCs is expected to obtain new antiviral drugs against HBV infection.
Starting Page	348
e-ISSN	19994915
DOI	10.3390/v14020348
Journal	Viruses
Issue Number	2
Volume Number	14
Language	English
Publisher	MDPI
Publisher Date	2022-02-08
Access Restriction	Open
Subject Keyword	Viruses Virology Hepatitis B Virus Core Protein Capsid Assembly Modulator Antiviral Activity
Content Type	Text
Resource Type	Article

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