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Discovery of a New Sulfonamide Hepatitis B Capsid Assembly Modulator

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posted on 2020-01-15, 15:04 authored by Hyo Gyeong Na, Ali Imran, Kyuneun Kim, Hong Sik Han, Young Jin Lee, Myung-Jin Kim, Chang-Soo Yun, Young-Sik Jung, Joo-Youn Lee, Soo Bong Han
Hepatitis B virus (HBV) remains a major health concern with 260 million people having been infected globally, and approximately 680,000 deaths have occurred annually from cirrhosis and liver cancer. The modulation of HBV capsid assembly has emerged as a promising therapeutic approach for curing chronic HBV infection. Small-molecule capsid assembly modulators (CAMs) can broadly be classified as heteroaryldihydropyrimidines and sulfamoylbenzamides (SBAs). SBAs are capsid activators that inhibit viral replication by achieving capsid assembly before polymerase encapsulation. Herein, we report a novel series of HBV CAMs based on NVR 3-778, a potent CAM belonging to the SBA class. The lead compound (KR-26556) exhibited improved pharmacological activity and was examined through molecular docking studies.

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