Center for Advanced Biotechnology and Medicine, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Center for Advanced Biotechnology and Medicine, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Drug Discov Today. 2022 Jul;27(7):1832-1846. doi: 10.1016/j.drudis.2022.02.016. Epub 2022 Feb 23.
Infection with HIV can cripple the immune system and lead to AIDS. Hepatitis B virus (HBV) is a hepadnavirus that causes human liver diseases. Both pathogens are major public health problems affecting millions of people worldwide. The polymerases from both viruses are the most common drug target for viral inhibition, sharing common architecture at their active sites. The L-nucleoside drugs emtricitabine and lamivudine are widely used HIV reverse transcriptase (RT) and HBV polymerase (Pol) inhibitors. Nevertheless, structural details of their binding to RT(Pol)/nucleic acid remained unknown until recently. Here, we discuss the implications of these structures, alongside related complexes with L-dNTPs, for the development of novel L-nucleos(t)ide drugs, and prospects for repurposing them.
感染 HIV 会削弱免疫系统，导致艾滋病。乙型肝炎病毒 (HBV) 是一种嗜肝 DNA 病毒，可导致人类肝脏疾病。这两种病原体都是影响全球数百万人的主要公共卫生问题。两种病毒的聚合酶都是抑制病毒最常用的药物靶点，在其活性部位具有共同的结构。L-核苷药物恩曲他滨和拉米夫定是广泛用于 HIV 逆转录酶 (RT) 和 HBV 聚合酶 (Pol) 的抑制剂。然而，直到最近，它们与 RT(Pol)/核酸结合的结构细节仍然未知。在这里，我们讨论了这些结构，以及与 L-dNTP 相关的复合物，对开发新型 L-核苷（t）药物的意义，以及重新利用它们的前景。
