College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
Chem Biol Drug Des. 2011 Oct;78(4):709-17. doi: 10.1111/j.1747-0285.2011.01179.x. Epub 2011 Sep 6.
Neuraminidase (NA) is a major glycoprotein of influenza virus which is essential for viral infection. It offers a potential target for antiviral drug design and discovery. To develop novel potent neuraminidase inhibitors (NAI), Surflex-Dock was employed to dock 40 hydrophobic p-aminosalicylic acid derivatives into the active site of NA. The 3D-quantitative structure-activity relationship studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 40 molecules. Both CoMFA (q(2) = 0.628, r(2) = 0.697) and CoMSIA (q(2) = 0.746, r(2) = 0.816) gave reasonable results. A preliminary pharmacokinetic profile of these NAI was also performed on the basis of Volsurf predictions. The results obtained from this study will be useful in the design of novel potent NAI.
神经氨酸酶（NA）是流感病毒的主要糖蛋白，对病毒感染至关重要。它为抗病毒药物的设计和发现提供了一个潜在的目标。为了开发新型有效的神经氨酸酶抑制剂（NAI），我们采用 Surflex-Dock 将 40 种疏水性对氨基水杨酸衍生物对接入 NA 的活性部位。对 40 个分子进行了三维定量构效关系研究，包括比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）。CoMFA（q2=0.628，r2=0.697）和 CoMSIA（q2=0.746，r2=0.816）都给出了合理的结果。还根据 Volsurf 预测对这些 NAI 的初步药代动力学特征进行了研究。这项研究的结果将有助于设计新型有效的 NAI。
