Sharma Anil K, George Varghese, Valiathan Ranjini, Pilakka-Kanthikeel Sudheesh, Pallikkuth Suresh
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA, USA.
Recent Pat Inflamm Allergy Drug Discov. 2013 May;7(2):151-61. doi: 10.2174/1872213x11307020006.
Advances in the drug development against HIV-1 have lead to the identification of new compounds which could be used to target cellular entry and nuclear integration of virus in addition to drugs that commonly target reverse transcriptase and protease. These additional targets have added a new dimension to fight against HIV. Cellular entry of HIV is a multistep procedure involving a range of cellular and molecular interactions between virus envelope protein and receptors expressed on the surface of the target cells, thus providing many opportunities to block infection. Some of these entry inhibitors are currently being used in the clinic and more compounds are under various stages of development. Integration of the HIV-1 DNA is required and essential to maintain the viral DNA in the infected cell. The design and discovery of integrase inhibitors were first focused at targeting the catalytic site of integrase that selectively acting on strand transfer and thus inhibits integration of virus DNA with host cell genome. Thus, entry and integrase inhibitors present a real added value in combined treatment against HIV infection. This review discusses the recent development in the discovery of inhibitors of HIV entry and integration along with some of recent patents in the field.
抗HIV-1药物研发的进展已促成新化合物的发现，除了常用的针对逆转录酶和蛋白酶的药物外，这些新化合物可用于靶向病毒的细胞进入和核整合。这些额外的靶点为抗击HIV增添了新维度。HIV的细胞进入是一个多步骤过程，涉及病毒包膜蛋白与靶细胞表面表达的受体之间一系列细胞和分子相互作用，从而提供了许多阻断感染的机会。目前一些这类进入抑制剂正在临床中使用，更多化合物正处于不同的研发阶段。HIV-1 DNA的整合对于将病毒DNA维持在受感染细胞中是必需且至关重要的。整合酶抑制剂的设计与发现最初聚焦于靶向整合酶的催化位点，该位点选择性作用于链转移，从而抑制病毒DNA与宿主细胞基因组的整合。因此，进入抑制剂和整合酶抑制剂在联合治疗HIV感染方面具有实际的附加价值。本综述讨论了HIV进入和整合抑制剂发现方面的最新进展以及该领域的一些近期专利。
