Structure-based design and biochemical evaluation of sulfanilamide derivatives as hepatitis B virus capsid assembly inhibitors.
Virus capsid structure is essential in virion maturation and durability, so disrupting capsid assembly could be an effective way to reduce virion count and cure viral diseases. However, currently there is no known antiviral which affects capsid inhibition, and only a small number of assembly inhibitors were experimentally successful. In this present study, we aimed to find hepatitis B virus (HBV) capsid assembly inhibitor which binds to the HBV core protein and changes protein conformation. Several candidate molecules were found to bind to certain structure in core protein with high specificity. Furthermore, these molecules significantly changed the protein conformation and reduced assembly affinity of core protein, leading to decrease of the number of assembled capsid or virion, both in vitro and in vivo. In addition, prediction also suggests that improvements in inhibition efficiency could be possible by changing functional groups and ring structures.
Department of Biological Sciences, Seoul National University , Seoul , Republic of Korea.
Min-Hyung
MH
Cho
Jin-Su
JS
Song
Hie-Joon
HJ
Kim
Sung-Gyoo
SG
Park
Guhung
G
Jung
D002213:Capsid / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D015195:Drug Design; D006515:Hepatitis B virus / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019065:Virus Assembly / Q000187:drug effects
D013424:Sulfanilamides; D000077145:Sulfanilamide