Novel therapeutic strategies targeting HIV integrase

BMC Medicine

Mark A Wainberg²  Richard D Sloan¹  Peter K Quashie³ 

[1]McGill University AIDS Centre, Lady Davis Institute, Montreal, Canada

[2]Department of Microbiology and Immunology, McGill University, Montreal, Canada

[3]Division of Experimental Medicine, McGill University, Montreal, Canada

关键词: resistance;    raltegravir;    new drugs;    mutations;    HIV integrase;    dolutegravir;    crystal structure;   

Others  :  1126268
DOI  :  10.1186/1741-7015-10-34

 received in 2011-12-05, accepted in 2012-04-12,  发布年份 2012

【 摘 要 】

Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds.

【 授权许可】

   
2012 Quashie et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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