Naturally occurring Vpr inhibitors from medicinal plants of Myanmar
Naturally occurring Vpr inhibitors from medicinal plants of Myanmar
复制标题
来自缅甸药用植物的天然 Vpr 抑制剂
DOI：
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发表时间：
2017
影响因子：
3.3
通讯作者：
H. Morita
中科院分区：
文献类型：
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作者：
N. Win;Hla Ngwe;I. Abe;H. Morita
人类免疫缺陷病毒1型（HIV-1）是慢病毒家族成员，其编码逆转录病毒Gag、Pol和Env蛋白，以及沿着六种另外的辅助蛋白，达特、Rev、Vpu、Vif、Nef和Vpr。目前批准的抗HIV药物靶向Pol和Env编码蛋白。然而，这些药物仅在减少病毒复制方面有效。此外，药物的毒性和耐药菌株的出现已成为严重的世界性问题。耐药性最终会对所有已批准的抗HIV药物产生，包括新批准的靶向HIV整合酶（IN）的药物。抗药性的出现可能是因为病毒复制过程中发生的自发突变。因此，必须开发有效阻断其他病毒成分的新药，以降低耐药率并抑制病毒复制，同时具有很小或没有长期毒性。辅助蛋白可以扩大治疗选择。病毒蛋白R（Vpr）是HIV辅助蛋白中最有前途的药物靶点之一。然而，在抗HIV药物的发现中，对抑制剂的研究仍在继续。在这篇综述中，我们总结了从两种缅甸药用植物中发现的天然存在的化合物以及它们的构效关系。从美丽山奈根茎和爪哇苦豆树皮中共分离得到49个次生代谢产物，经鉴定分别为异海松烷型二萜和苦木烷型苦木素。其中，7个二萜类和15个苦木类被发现是Vpr抑制剂缺乏可检测的毒性，其效力根据各自的功能而变化。
Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs’ toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN). Drug resistance likely emerges because of spontaneous mutations that occur during viral replication. Therefore, new drugs that effectively block other viral components must be developed to reduce the rate of resistance and suppress viral replication with little or no long-term toxicity. The accessory proteins may expand treatment options. Viral protein R (Vpr) is one of the promising drug targets among the HIV accessory proteins. However, the search for inhibitors continues in anti-HIV drug discovery. In this review, we summarize the naturally occurring compounds discovered from two Myanmar medicinal plants as well as their structure-activity relationships. A total of 49 secondary metabolites were isolated from Kaempferia pulchra rhizomes and Picrasama javanica bark, and the types of compounds were identified as isopimarane diterpenoids and picrasane quassinoids, respectively. Among the isolates, 7 diterpenoids and 15 quassinoids were found to be Vpr inhibitors lacking detectable toxicity, and their potencies varied according to their respective functionalities.