AI Article Synopsis
- Scientists are looking for new ways to treat chronic hepatitis B by targeting something called the nucleocapsid, which helps the virus replicate.
- They found small molecules called sulfonylpiperidine-3-carboxamides (SPCs) that can stop the virus from spreading by reducing the amount of HBV DNA in the body.
- One specific SPC named C-39 was discovered to be very effective against the virus without harming healthy cells, making it a promising candidate for developing new antiviral medicines.
Article Abstract
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, -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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876525 | PMC |
| http://dx.doi.org/10.3390/v14020348 | DOI Listing |
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