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Researchers used deep-learning algorithms and coevolution analysis to predict how hepatitis B virus proteins interact during cell infection, specifically mapping interactions between the viral capsid protein and envelope proteins. The study identified potential protein-protein interaction hotspots and compared computational predictions with existing experimental data, including NMR studies showing how certain peptides can block core-envelope interactions. This work provides new insights into the molecular mechanisms of how hepatitis B virus assembles its envelope around its core structure.
Why it matters
Understanding the precise protein interactions involved in hepatitis B virus assembly could enable development of new antiviral therapies that disrupt these critical steps in the viral life cycle. The identified interaction sites represent potential drug targets for treating the estimated 250 million people worldwide living with chronic hepatitis B infection.
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⚠️ Preprint – Noch nicht peer-reviewed
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We here predicted the interactions between the capsid (Cp) and envelope proteins (S/M/LHBs) of the hepatitis B virus using a recently established mutation-driven deep-learning model, as well as coevolution signatures that serve as markers of physical interactions and/or functional relationships. The sequence-based analyses reveal putative protein-protein interaction (PPI) hotspots in proteins, and identify abundant coevolved residues within and across proteins. We analyze the results with a focus on the intermolecular interactions between Cp and the large envelope protein LHBs, especially its disordered preS domain. We compare the predicted PPI interface sites to previous evidence on PPIs, derived from mutational analyses described in the literature. We equally integrate experimental NMR data that provide a rationale for the previous observation that spike-binding peptides inhibit core-envelope interactions. Our work sheds new light on the molecular mechanisms at play on HBV envelopment, and provides starting points for the experimental investigation of these interactions using structural and molecular virology approaches.