In silico study on baicalein and baicalin as inhibitors of dengue virus replication
In silico study on baicalein and baicalin as inhibitors of dengue virus replication
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DOI：
10.1039/c6ra00817h
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发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Zandi, Keivan
中科院分区：
文献类型：
--
作者：
Hassandarvish, Pouya;Rothan, Hussin A.;Zandi, Keivan
登革病毒（DENV）是一种重要的人类虫媒病毒，属于黄病毒科。目前，没有针对DENV的疫苗或有效的抗病毒剂。因此，找到一种有效的抗病毒药物对这种病毒至关重要。我们以前曾报道过两种黄酮类化合物，即黄芩素和黄芩苷，在Vero细胞中对病毒复制周期的不同阶段的抗DENV活性。在这项研究中，我们的目的是预测对DENV复制重要的病毒蛋白与这两种黄酮类化合物之间可能的相互作用，作为具有已知体外抗DENV活性的抗DENV药物发现的潜在候选物。在这项研究中，使用适当的软件预测感兴趣的化合物与DENV的三个重要蛋白质之间的相互作用。此外，这些化合物和选定的蛋白质之间的结合能计算作为分子对接研究的主要标准之一。结果表明，两种感兴趣的化合物作为配体，可以通过氢键和其他相互作用如π-π相互作用、π-σ相互作用和π-阳离子相互作用与作为受体的所选病毒蛋白结合。所得数据显示测试化合物与DENV的NS 2B-NS 3蛋白酶之间的显著亲和力。因此，进行体外抗蛋白酶测定，结果显示两种化合物，尤其是黄芩素具有显著的抗DENV蛋白酶活性。总之，我们获得的数据表明，两种测试化合物都可以影响DENV细胞内复制和内化。然而，这些结果支持了我们以前在体外研究中的发现，并鼓励我们进一步研究这些化合物的作用机制。
The dengue virus (DENV) is an important human arbovirus that belongs to the Flaviviridae. Currently, there is no vaccine or effective antiviral agent against DENV. Therefore, finding an efficient antiviral agent against this virus is crucial. We have previously reported the anti-DENV activity of two flavonoids, namely, baicalein and baicalin, against different stages of the virus replication cycle in Vero cells. In this study, we aimed to predict the possible interactions between viral proteins that are important for DENV replication and these two flavonoids as potential candidates for anti-DENV drug discovery with known in vitro anti-DENV activity. In this study, the interactions between compounds of interest and three important proteins of DENV were predicted using appropriate software. Moreover, the binding energy between these compounds and selected proteins was calculated as one of the main criteria for molecular docking studies. The results showed that both compounds of interest, as ligands, can bind with chosen viral proteins, as receptors, through hydrogen bonding and other interactions such as pi-pi interactions, pi-sigma interactions and pi-cation interactions. The obtained data showed significant affinity between the tested compounds and the NS2B-NS3 protease of DENV. Therefore, an in vitro anti-protease assay was conducted and the results showed significant anti-DENV protease activity for both compounds, especially baicalein. In conclusion, our obtained data showed that both tested compounds can affect DENV intracellular replication and internalization. However, these results support our previous findings from in vitro studies and encourage us to further studies towards finding the mechanism of action of these compounds.