Open AccessA pocket-factor–triggered conformational switch in the hepatitis B virus capsid
Author(s) -
Lauriane Lecoq,
Shishan Wang,
Marie Dujardin,
Peter Jan Zimmermann,
Leonard Schuster,
MarieLaure Fogeron,
Mathilde Briday,
Maarten Schledorn,
Thomas Wiegand,
Laura Cole,
Roland Montserret,
Stéphane Bressanelli,
Beat H. Meier,
Michael Nassal,
Anja Böckmann
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022464118
Subject(s) - capsid , virology , hepatitis b virus , virus , biology
Significance Viral hepatitis causes more deaths than tuberculosis and HIV-1 infection. Most cases are due to chronic infection with hepatitis B virus (HBV), which afflicts >250 million people. Current therapies are rarely curative, and new approaches are needed. Here, we report the discovery (by nuclear magnetic resonance) of a small molecule binder in the hydrophobic pocket in the HBV capsid. This structural element is, in an unknown manner, central in capsid envelopment. Binding of the pocket factor induces a distinct, stable conformation in the capsid, as expected for a signaling switch. This brings not only a new molecular view on the mechanism underlying capsid envelopment, but it also opens a rationale for its inhibition.