National Academy of Sciences, Proceedings of the National Academy of Sciences, 17(118), 2021
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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.