Background: Ixora coccinea is a tropical ornamental shrub employed in ethnomedicine for the treatment of a number of diseases none of which include the Human Immunodeficiency Virus (HIV) infection. Ixoratannin A-2, one of the constituents, was previously identified via virtual-screening and experimentally confirmed to possess significant anti-HIV-1 activity in an in vitro CD4+ replication assay. This activity was observed to be significantly reduced in degree in viruses lacking the protein Vpu. This suggests the involvement of Vpu as well as other extra-Vpu macromolecules in its antiviral activity.

Methods: In the present computational search for the identity of the other macromolecules that could possibly explain the observed activity, a panel of fourteen established HIV-1 macromolecular targets was assembled against which ixoratannin A-2 and other major phytoconstituents of I. coccinea were virtually screened.

Results: Structural analyses of the computed ligand-bound complexes, as well as the careful investigation of the thermodynamic attributes of the predicted binding, revealed subtle selectivity patterns at the atomistic level that suggest the likely involvement of multiple macromolecular processes. Some of the binding interactions were found to be thermodynamically favourable, including the multidrug-resistant HIV protease enzyme, CXCR4 and the human elongin C protein all of which formed reasonably strong interactions with ixoratannin A-2 and other constituents of I. coccinea.

Conclusion: Ixoratannin A-2’s ability to favourably interact with multiple HIV-1 and human targets could explain its observed extra-Vpu antiviral activity. This, however, does not imply uncontrolled binding with all available targets; on the other hand, molecular size of ixoratannin A-2 and combination of functional groups confer on it a decent level of selectivity against many of the investigated HIV/AIDS targets.

背景：Ixora coccinea是一种用于民族药的热带观赏灌木，用于治疗许多疾病，其中包括人类免疫缺陷病毒（HIV）感染。成分之一伊索拉坦宁A-2先前已通过虚拟筛选进行了鉴定，并在体外CD4 +复制试验中经实验证实具有显着的抗HIV-1活性。在缺乏蛋白Vpu的病毒中，观察到该活性的程度显着降低。这表明Vpu以及其他超Vpu大分子参与了其抗病毒活性。

方法：在目前的计算中寻找可能解释所观察到的活性的其他大分子的身份时，组装了一个由十四个既定的HIV-1大分子靶标组成的小组，针对这些靶点而言，艾克索拉坦宁A-2和其他主要的I.coccinea植物组成筛选。

结果：对计算的配体结合的复合物的结构分析，以及对预期结合的热力学属性的仔细研究，揭示了在原子水平上微妙的选择性模式，表明可能涉及多个大分子过程。发现一些结合相互作用在热力学上是有利的，包括耐多药的HIV蛋白酶，CXCR4和人延伸蛋白C蛋白，所有这些都与ixoratannin A-2和I.coccinea的其他成分形成相当强的相互作用。

结论：伊索拉坦宁A-2与多种HIV-1和人类靶标良好相互作用的能力可以解释其观察到的Vpu外抗病毒活性。但是，这并不意味着与所有可用目标的不受约束的绑定；另一方面，ixoratannin A-2的分子大小和官能团的结合赋予了其对许多研究的HIV / AIDS目标的适度选择性。