HIV-1 Integrase Strand Transfer Inhibitors Stabilize an Integrase–Single Blunt-Ended DNA Complex
نویسندگان
چکیده
منابع مشابه
Integrase Strand Transfer Inhibitors in HIV Therapy
HIV drug resistance has been one of the major obstacles to HIV eradication and has contributed to the need for the constant development of new antiretroviral drugs over the past 25 years. With the recent approval of dolutegravir for human therapy by the U.S. Food and Drug Administration, health practitioners may soon have access to three integrase strand transfer inhibitors to treat individuals...
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Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients who fail dolutegravir treatment. Furthermore, most in vitro experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an in vitro dolutegrav...
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Integrase mutations can reduce the effectiveness of the first-generation FDA-approved integrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG). The second-generation agent, dolutegravir (DTG), has enjoyed considerable clinical success; however, resistance-causing mutations that diminish the efficacy of DTG have appeared. Our current findings support and extend the...
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HIV integrase (IN) strand transfer inhibitors (INSTIs) are among the newest anti-AIDS drugs; however, mutant forms of IN can confer resistance. We developed noncytotoxic naphthyridine-containing INSTIs that retain low nanomolar IC50 values against HIV-1 variants harboring all of the major INSTI-resistant mutations. We found by analyzing crystal structures of inhibitors bound to the IN from the ...
متن کاملHIV-1 Integrase Strand Transfer Inhibitors: Novel Insights into their Mechanism of Action.
Human immunodefi ciency virus type-1 integrase (IN) is a new and novel target for inhibitors. Strand transfer inhibitors effectively prevent concerted integration of viral DNA by IN into the host chromosomes. Raltegravir is the fi rst approved strand transfer inhibitor for the treatment of HIV-1/AIDS. We propose a mechanistic hypothesis as to "when and where" these inhibitors are active in viru...
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ژورنال
عنوان ژورنال: Journal of Molecular Biology
سال: 2011
ISSN: 0022-2836
DOI: 10.1016/j.jmb.2011.01.043