Assembly-directed antivirals differentially bind quasi-equivalent pockets to modify HBV capsid tertiary and quaternary structure
Hepatitis B Virus (HBV) is a major cause of liver disease. Assembly of the HBV capsid is a critical step in virus production and an attractive target for new antiviral therapies. We determined the structure of HBV capsid in complex with AT-130, a member of the phenylpropenamide family of assembly ef...
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Veröffentlicht in: | Structure (London) 2013-07, Vol.21 (8), p.1406-1416 |
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Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Hepatitis B Virus (HBV) is a major cause of liver disease. Assembly of the HBV capsid is a critical step in virus production and an attractive target for new antiviral therapies. We determined the structure of HBV capsid in complex with AT-130, a member of the phenylpropenamide family of assembly effectors. AT-130 causes tertiary and quaternary structural changes, but does not disrupt capsid structure. AT-130 binds a hydrophobic pocket that also accommodates the previously characterized HAP compounds, but favors a unique quasi-equivalent location on the capsid surface. Thus, this pocket is a promiscuous drug binding site and a likely target for different assembly effectors with a broad range of mechanisms of activity. That AT-130 successfully decreases virus production by increasing capsid assembly rate without disrupting capsid structure delineates a new paradigm in antiviral design, that disrupting reaction timing is a viable strategy for assembly effectors of HBV and other viruses. |
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ISSN: | 0969-2126 1878-4186 |
DOI: | 10.1016/j.str.2013.06.013 |