Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition.
Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition.
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DOI：
10.1016/j.jmb.2008.10.071
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发表时间：
2009-01-23
影响因子：
5.6
通讯作者：
Arnold, Eddy
中科院分区：
文献类型：
--
作者：
Sarafianos, Stefan G.;Marchand, Bruno;Das, Kalyan;Himmel, Daniel M.;Parniak, Michael A.;Hughes, Stephen H.;Arnold, Eddy
HIV-1的快速复制和病毒复制过程中的错误导致病毒在患者体内迅速进化，使疫苗开发和药物治疗的问题特别具有挑战性。在缺乏有效疫苗的情况下，药物是唯一有效的治疗方法。抗艾滋病毒药物起作用;迄今为止，药物治疗已经挽救了300多万年的生命。不幸的是，HIV-1对所有可用的药物都产生了抗药性。尽管许多有用的抗HIV药物已被批准用于患者，但与药物毒性和耐药性发展相关的问题意味着寻找新药是一个持续的过程。三种病毒酶，逆转录酶（RT），整合酶（IN）和蛋白酶（PR）都是很好的药物靶点。两种不同类型的逆转录酶抑制剂，这两种抑制剂都阻断了逆转录酶的聚合酶活性，已被批准用于治疗HIV-1感染，核苷类似物（NRTI）和非核苷（NNRTI），并且有希望的化合物，无论是阻断RNA酶H活性还是以其他方式阻断聚合酶。对RT的结构和功能以及抑制机制的更好理解可用于产生更好的药物;特别是对当前HIV-1耐药株有效的药物。
The rapid replication of HIV-1 and the errors made during viral replication, cause the virus to evolve rapidly in patients, making the problems of vaccine development and drug therapy particularly challenging. In the absence of an effective vaccine, drugs are the only useful treatment. Anti-HIV drugs work; so far drug therapy has saved more than three million years of life. Unfortunately, HIV-1 develops resistance to all of the available drugs. Although a number of useful anti-HIV drugs have been approved for use in patients, the problems associated with drug toxicity and the development of resistance means that the search for new drugs is an ongoing process. The three viral enzymes, reverse transcriptase (RT), integrase (IN), and protease (PR) are all good drug targets. Two distinct types of RT inhibitors, both of which block the polymerase activity of RT, have been approved to treat HIV-1 infections, nucleoside analogs (NRTIs) and nonnucleosides (NNRTIs), and there are promising leads for compounds that either block the RNase H activity or block the polymerase in other ways. A better understanding of the structure and function(s) of RT and of the mechanism(s) of inhibition can be used to generate better drugs; in particular drugs that are effective against the current drug-resistant strains of HIV-1.
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影响因子：
56.9
作者：
COFFIN, JM
通讯作者：
COFFIN, JM
影响因子：
4.8
作者：
Arion, D;Sluis-Cremer, N;Parniak, MA
通讯作者：
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影响因子：
5.4
作者：
Boyer, PL;Sarafianos, SG;Hughes, SH
通讯作者：
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影响因子：
6.4
作者：
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影响因子：
2.9
作者：
Arion, D;Kaushik, N;Parniak, MA
通讯作者：
Parniak, MA