School of Biotechnology, Ho Chi Minh International University, Quarter 6, Linh Trung, Thu Duc District, Ho Chi Minh City 70000, Vietnam.
Molecules. 2011 Dec 8;16(12):10227-55. doi: 10.3390/molecules161210227.
The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF) and 2009-H1N1 (Genbank accession number GQ385383) viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.
流感 A 病毒膜上的 M2 通道蛋白已成为金刚烷胺和金刚乙胺等抗流感药物的主要靶标。H3N2（PDB 代码 2RLF）和 2009-H1N1（Genbank 登录号 GQ385383）病毒的 M2 通道蛋白结构可能有助于研究人员解决这两种基于金刚烷的药物的耐药性问题，并开发更强大的抗流感 A 病毒新药。在本研究中，我们通过结合不同的计算方法，包括对接和药效团建模的虚拟筛选，寻找新的 M2 通道抑制剂。虚拟筛选用于计算受体 M2 通道蛋白与 200 种新设计的配体之间的结合自由能。之后，药效团分析用于识别与 M2 蛋白相互作用的重要抑制剂和与 M2 通道蛋白结合的顶级化合物的共同特征。最后，确定了两种最有潜力的化合物作为新型抑制剂，以抑制 H3N2 和 2009-H1N1 流感 A 病毒中的 M2 通道蛋白。
