Saeed Umar, Piracha Zahra Zahid, Alrokayan Salman, Hussain Tajamul, Almajhdi Fahad N, Waheed Yasir
Clinical and Biomedical Research Center (CBRC) and Multidisciplinary Laboratory (MDL), Foundation University Islamabad, Islamabad 44000, Pakistan.
Department of Microbiology, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.
Microorganisms. 2023 Nov 21;11(12):2826. doi: 10.3390/microorganisms11122826.
The Hepatitis B virus (HBV) HBx and HBc proteins play a crucial role in associating with covalently closed circular DNA (cccDNA), the primary factor contributing to intrahepatic viral persistence and a major obstacle in achieving a cure for HBV. The cccDNA serves as a reservoir for viral persistence. Targeting the viral HBc and HBx proteins' interaction with cccDNA could potentially limit HBV replication. In this study, we present epitopes identified from global consensus sequences of HBx and HBc proteins that have the potential to serve as targets for the development of effective vaccine candidates. Furthermore, conserved residues identified through this analysis can be utilized in designing novel, site-specific anti-HBV agents capable of targeting all major genotypes of HBV. Our approach involved designing global consensus sequences for HBx and HBc proteins, enabling the analysis of variable regions and highly conserved motifs. These identified motifs and regions offer potent sites for the development of peptide vaccines, the design of site-specific RNA interference, and the creation of anti-HBV inhibitors. The epitopes derived from global consensus sequences of HBx and HBc proteins emerge as promising targets for the development of effective vaccine candidates. Additionally, the conserved residues identified provide valuable insights for the development of innovative, site-specific anti-HBV agents capable of targeting all major genotypes of HBV from A to J.
乙肝病毒（HBV）的X蛋白（HBx）和核心蛋白（HBc）在与共价闭合环状DNA（cccDNA）的关联中起着关键作用，cccDNA是导致肝内病毒持续存在的主要因素，也是实现乙肝治愈的主要障碍。cccDNA是病毒持续存在的储存库。靶向病毒HBc和HBx蛋白与cccDNA的相互作用可能会限制乙肝病毒的复制。在本研究中，我们展示了从HBx和HBc蛋白的全球共识序列中鉴定出的表位，这些表位有潜力作为开发有效候选疫苗的靶点。此外，通过该分析鉴定出的保守残基可用于设计新型的、位点特异性的抗乙肝病毒药物，这些药物能够靶向所有主要基因型的乙肝病毒。我们的方法包括设计HBx和HBc蛋白的全球共识序列，以便分析可变区和高度保守的基序。这些鉴定出的基序和区域为肽疫苗的开发、位点特异性RNA干扰的设计以及抗乙肝病毒抑制剂的创制提供了有力位点。源自HBx和HBc蛋白全球共识序列的表位成为开发有效候选疫苗的有前景的靶点。此外，鉴定出的保守残基为开发能够靶向从A到J所有主要基因型乙肝病毒的创新型、位点特异性抗乙肝病毒药物提供了有价值的见解。
