乙型肝炎病毒(hepatitis B virus,HBV)感染是严重威胁人类健康的全球性健康问题,它与肝硬化和肝细胞癌的发展有关,并能引发不同类型的肝损伤.令人遗憾的是,目前尚未实现慢性乙型肝炎(chronic hepatitis B,CHB)的功能性治愈.在深入研究HBV不同蛋白与其配体间的相互作用后发现:特定配体与关键氨基酸的相互作用,实则扮演着化合物抗HBV效力的"开关".基于这一发现,运用分子对接技术,对蛋白与配体之间的结合模式进行分析.通过对比分析不同配体小分子间的相似之处,成功锁定了具有潜力的药效团,并进一步探讨了氨基酸与这些化合物间可能存在的相互作用.这些研究不仅深化了对HBV衣壳蛋白装配调节剂(capsid assembly modulator,CAM)结构多样性的理解,更在药效团类似性方面取得了新的认识,为抗病毒药物的合理设计提供思路.
Assembly Modulator of Hepatitis B Virus Capsid Protein and Its Inspiration for Drug Design
Hepatitis B virus infection is a global health problem that seriously threatens human health.It is related to the development of liver cirrhosis and hepatocellular carcinoma,and can cause different types of liver damage.Unfortunately,there has been no accomplished functional cure in chronic hepatitis B(CHB)to date.After in-depth study of the interactions between different HBV proteins and their ligands,it was found that the interaction between specific ligands and key amino acids actually acts as a"switch"for the anti-HBV potency of a compound.Based on this finding,molecular docking technology was applied to analyze the binding mode between the protein and the ligand.By comparing and analyzing the similarities between the small molecules of different ligands,the potential pharmacophores were successfully determined,and the possible interactions between amino acids and these compounds were further explored.These studies not only deepen our understanding of the diversity of shape and structure of HBV capsid assembly modulator(CAM),but also enable us to obtain a new understanding of pharmacophore similarity,which provides some insight for rational design of antiviral drugs.
hepatitis B viruscapsid assembly modulatormolecular dockingpharmacophoredrug design
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