Issue 28, 2015

Hepatitis B virus peptide inhibitors: solution structures and interactions with the viral capsid

Abstract

Hepatitis B virus (HBV) infection remains a health problem globally despite the availability of effective vaccines. In the assembly of the infectious virion, both the preS and S regions of the HBV large surface antigen (L-HBsAg) interact synergistically with the viral core antigen (HBcAg). Peptides preS and S based on the L-HBsAg were demonstrated as potential inhibitors to block the viral assembly. Therefore, the objectives of this study were to determine the solution structures of these peptides and study their interactions with HBcAg. The solution structures of these peptides were solved using 1H, 13C, and 15N NMR spectroscopy. Peptide preS has several structured regions of β-turns at Ser7-Pro8-Pro9, Arg11-Thr12-Thr13 and Ser22-Thr23-Thr24 sequences whereas peptide S has only one structured region observed at Ser3-Asn4-His5. Both peptides contain bend-like structures surrounding the turn structures. Docking studies revealed that both peptides interacted with the immunodominant region of HBcAg located at the tip of the viral capsid spikes. Saturation Transfer Difference (STD) NMR experiments identified several aromatic residues in peptides preS and S that interact with HBcAg. This study provides insights into the contact regions of L-HBsAg and HBcAg at atomic resolution which can be used to design antiviral agents that inhibit HBV morphogenesis.

Graphical abstract: Hepatitis B virus peptide inhibitors: solution structures and interactions with the viral capsid

Supplementary files

Article information

Article type
Paper
Submitted
06 Mar 2015
Accepted
11 Jun 2015
First published
11 Jun 2015

Org. Biomol. Chem., 2015,13, 7780-7789

Hepatitis B virus peptide inhibitors: solution structures and interactions with the viral capsid

A. Muhamad, K. L. Ho, Mohd. B. Abdul Rahman, B. A. Tejo, D. Uhrín and W. S. Tan, Org. Biomol. Chem., 2015, 13, 7780 DOI: 10.1039/C5OB00449G

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