Resistance to Integrase Inhibitors

Viruses

Mathieu Métifiot¹  Christophe Marchand¹  Kasthuraiah Maddali¹ 

[1] >Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA; E-Mails: [e-mail] (M.M.); [e-mail] (C.M.); [e-mail] (K.M

关键词: AIDS;    HIV-1 integrase;    Raltegravir;    Elvitegravir;    GSK-1349572;    GSK-1265744;    interfacial inhibitors;    resistance;   

DOI  :  10.3390/v2071347

来源: mdpi

【 摘 要 】

Integrase (IN) is a clinically validated target for the treatment of human immunodeficiency virus infections and raltegravir exhibits remarkable clinical activity. The next most advanced IN inhibitor is elvitegravir. However, mutant viruses lead to treatment failure and mutations within the IN coding sequence appear to confer cross-resistance. The characterization of those mutations is critical for the development of second generation IN inhibitors to overcome resistance. This review focuses on IN resistance based on structural and biochemical data, and on the role of the IN flexible loop i.e., between residues G140-G149 in drug action and resistance.

【 授权许可】

CC BY   
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