Recent Advances in the Development of Integrase Inhibitors for HIV Treatment

被引:24
作者
Trivedi, Jay [1 ,4 ]
Mahajan, Dinesh [3 ]
Jaffe, Russell J. [4 ]
Acharya, Arpan [4 ]
Mitra, Debashis [1 ,2 ]
Byrareddy, Siddappa N. [4 ,5 ,6 ]
机构
[1] Pune Univ Campus, Natl Ctr Cell Sci, Pune, Maharashtra, India
[2] Ctr DNA Fingerprinting & Diagnost, Hyderabad, Uppal Telangana, India
[3] NCR Biotech Sci Cluster, Translat Hlth Sci & Technol Inst, Drug Discovery Res Ctr, 3rd Milestone, Faridabad, Haryana, India
[4] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA
[5] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA
[6] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
关键词
HIV integration; Integrase inhibitors; Latent provirus; Retroviridae; Therapeutic application; ANTIRETROVIRAL-NAIVE ADULTS; STRAND TRANSFER INHIBITOR; ONCE-DAILY DOLUTEGRAVIR; REVERSE-TRANSCRIPTASE; ANTIVIRAL ACTIVITY; DOUBLE-BLIND; OPEN-LABEL; TENOFOVIR ALAFENAMIDE; RALTEGRAVIR TREATMENT; RESISTANCE PROFILE;
D O I
10.1007/s11904-019-00480-3
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose of the Review The complex multistep life cycle of HIV allows it to proliferate within the host and integrate its genome in to the host chromosomal DNA. This provirus can remain dormant for an indefinite period. The process of integration, governed by integrase (IN), is highly conserved across the Retroviridae family. Hence, targeting integration is not only expected to block HIV replication but may also reveal new therapeutic strategies to treat HIV as well as other retrovirus infections. Recent Findings HIV integrase (IN) has gained attention as the most promising therapeutic target as there are no equivalent homologues of IN that has been discovered in humans. Although current nano-formulated long-acting IN inhibitors have demonstrated the phenomenal ability to block HIV integration and replication with extraordinary half-life, they also have certain limitations. In this review, we have summarized the current literature on clinically established IN inhibitors, their mechanism of action, the advantages and disadvantages associated with their therapeutic application, and finally current HIV cure strategies using these inhibitors.
引用
收藏
页码:63 / 75
页数:13
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