The Spirocyclic Imine from a Marine Benthic Dinoflagellate, Portimine, Is a Potent Anti-Human Immunodeficiency Virus Type 1 Therapeutic Lead Compound
The Spirocyclic Imine from a Marine Benthic Dinoflagellate, Portimine, Is a Potent Anti-Human Immunodeficiency Virus Type 1 Therapeutic Lead Compound
复制标题
DOI：
10.3390/md17090495
复制
发表时间：
2019-09-01
期刊：
影响因子：
5.4
通讯作者：
Kubo, Yoshinao
中科院分区：
文献类型：
--
作者：
Izumida, Mai;Suga, Koushirou;Kubo, Yoshinao
在这项研究中，我们旨在从低等海洋动物中寻找具有防御人类免疫缺陷病毒1型（HIV-1）作用的化学物质。利用荧光素酶编码的HIV-1载体对80个化合物组成的海洋天然产物库进行了抗HIV-1感染活性筛选。在载体接种的细胞中，我们发现了五种降低荧光素酶活性的化合物。特别是，从底栖鞭毛藻Vulcanodinium rugosum中分离出的portinine具有显著的抗hiv -1活性。波替明抑制病毒感染的50%抑制浓度（IC50）值为4.1 nM，浓度低于200 nM时对宿主细胞无细胞毒作用。波替明还能抑制水疱性口炎病毒糖蛋白(VSV-G)-假型HIV-1载体感染。结果表明，portinine主要靶向HIV-1 Gag或Pol蛋白。为了分析portinine影响哪些复制步骤，用半定量PCR扩增了总DNA中的荧光素酶序列。该分析表明，波替明在逆转录步骤之前或在逆转录步骤中抑制HIV-1载体感染。通过体外逆转录酶测定，波替明也被证明对逆转录酶有直接影响。波替明有效地抑制HIV-1复制，是开发针对HIV-1诱导疾病的新型治疗药物的有力先导化合物。
In this study, we aimed to find chemicals from lower sea animals with defensive effects against human immunodeficiency virus type 1 (HIV-1). A library of marine natural products consisting of 80 compounds was screened for activity against HIV-1 infection using a luciferase-encoding HIV-1 vector. We identified five compounds that decreased luciferase activity in the vector-inoculated cells. In particular, portimine, isolated from the benthic dinoflagellate Vulcanodinium rugosum, exhibited significant anti-HIV-1 activity. Portimine inhibited viral infection with an 50% inhibitory concentration (IC50) value of 4.1 nM and had no cytotoxic effect on the host cells at concentrations less than 200 nM. Portimine also inhibited vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped HIV-1 vector infection. This result suggested that portimine mainly targeted HIV-1 Gag or Pol protein. To analyse which replication steps portimine affects, luciferase sequences were amplified by semi-quantitative PCR in total DNA. This analysis revealed that portimine inhibits HIV-1 vector infection before or at the reverse transcription step. Portimine has also been shown to have a direct effect on reverse transcriptase using an in vitro reverse transcriptase assay. Portimine efficiently inhibited HIV-1 replication and is a potent lead compound for developing novel therapeutic drugs against HIV-1-induced diseases.