Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Theoretical and Natural Science
Vol. 21, 20 December 2023
Open
Access | Article
Binding modes in ligand-docked hepatitis B virus core protein simulated by a Monte Carlo method
* Author to whom correspondence should be addressed.
Abstract
Hepatitis B virus core protein (HBV Cp) is closely involved in the viral assembly, nuclear functions, compartment for reverse transcription, and intra-cellular trafficking. Therefore, modulation of HBV Cp assembly is a promising method to control HBV infection in both preclinical and clinical studies. In this paper, two ligands of HAP18 and AT-130, as representations of heteroaryldihydropyrimidines and phenylpropenamides, have been chosen. Their Binding modes and conformations docking with the HBV Cp have been simulated by a Monte Carlo method. Strong polar contact in HAP18-bound and relatively weak interaction dominated by the Lennard-Jones potential in AT130-bound have been observed, respectively. Although different binding modes result in different assembly behaviors of HBV core protein, both of them strongly influence the quaternary structure of the Cp assembly, changing the spatial relationship between dimers, and inducing noninfective Cp misassembly. The simulation is expected to be helpful to get some insight into the antiviral mechanism of HBV Cp assembly modulation.
Keywords
hepatitis B virus core protein, HAP18, AT-130, capsid assembly modulation, binding modes
References
1. Publication WHO. “Hepatitis B vaccines: WHO position paper—recommendations.” Vaccine 28:589 –590 (2010).
2. Seto,W.-K.; Lo, Y.-R.; Pawlotsky, J.-M.; Yuen, M.-F. “Chronic hepatitis B virus infection.” Lancet, 392, 2313–2324 (2018).
3. Zlotnick A, Venkatakrishnan B, Tan Z, et al. “Core protein: a pleiotropic keystone in the HBV lifecycle.” Antiviral Res 121,82–93 (2015).
4. Kang JA, Kim S, Park M, et al. “Ciclopirox inhibits hepatitis B virus secretion by blocking capsid assembly.” Nat Commun, 10(1), 2184 (2019).
5. Lahlali T, Berke JM, Vergauwen K, et al. “Novel potent capsid assembly modulators regulate multiple steps of the hepatitis B virus life cycle.” Antimicrob Agents Chemother, 62(10), e00835-18 (2018).
6. Viswanathan, U.; Mani, N.; Hu, Z.; et al., “Targeting the multifunctional HBV core protein asa potential cure for chronic hepatitis B.” Antivir. Res., 182, 104917 (2020).
7. Taylor R. D., Jewsbury P. J. and Essex J. W. “A review of protein-small molecule docking methods.” J. Computer-Aided Mol. Design, 16: 151–166, (2002)
8. Wynne S A , Crowther R A , Leslie A G, “The crystal structure of the human hepatitis B virus capsid,” Mol Cell. 3(6):771-80 (1999).
9. Bourne C, Lee S, Venkataiah B, et al. “Small-molecule effectors of hepatitis B virus capsid assembly give insight into virus life cycle.” J Virol 82:10262–10270 (2008).
10. Katen SP, Tan Z, Chirapu SR, et al. “Assembly －directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary and quaternary structure.” Structure, 21 (8): 1406-1416 (2013).
Data Availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).
- Volume Title
- Proceedings of the 3rd International Conference on Biological Engineering and Medical Science
- ISBN (Print)
- 978-1-83558-215-2
- ISBN (Online)
- 978-1-83558-216-9
- Published Date
- 20 December 2023
- Series
- Theoretical and Natural Science
- ISSN (Print)
- 2753-8818
- ISSN (Online)
- 2753-8826
- DOI
- 10.54254/2753-8818/21/20230813
- Copyright
- 20 December 2023
- Open Access
- This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited