以SARS冠状病毒和人冠状病毒为代表的，细胞质内复制的冠状病毒主要感染人、禽、畜，与人类社会密切接触，造成巨大威胁和经济损失。我们研究发现SARS冠状病毒非结构蛋白nsp14和nsp16/nsp10复合体分别具有N7－和2'-O-甲基转移酶活性，参与病毒RNA的5'端加帽过程，是病毒RNA帽子合成的必须蛋白之一，影响病毒RNA的稳定，病毒蛋白翻译，参与病毒免疫逃逸等方面，是理想的抗病毒药物靶点。本研究将在前期的研究工作基础上，继续通过生物信息学预测，设计并大量筛选抑制冠状病毒RNA加帽酶功能的各种小分子化合物。结合体外生化活性实验，深入研究抑制剂的工作机理，并在细胞及动物模型上验证其抑制效应。这些研究将有利于我们高开发特异抗病毒药物，且具有较高的推广及应用潜力，也可用于其他细胞质内复制的RNA病毒的药物开发，对病毒病的防治提供依据。

RNA viruses which replicate and transcribe in cytoplasm, such as coronaviruses, infect human, bird, livestock, and closely contact with human society, cause a great threat and economic loss. We found that nonstructural protein nsp14 and nsp16 / Nsp10 complex of SARS coronavirus (SARS-CoV) possess N7- and 2'- O- methyl transferase activity, which involved in viral RNA 5' end capping process. These viral RNA capping enzymes are important to viral RNA stability, viral protein translation, viral immune escape and many other aspects. This study will focuse on the coronaviridae virus critical enzymes as potential drug targets. Based on our previous work, we are planning to screen small molecular compounds which inhibit the activities of coronavirus RNA capping enzymes, through bioinformatics prediction and yeast genetic screenning system in vivo. And biochemical assays in vitro will be use to illuminate the mechanisms of these inhibitors, further revealing viral RNA cap mechanism. Finally, cell and animal models will be use to validate the inhibition efficiency. These studies will promote the development of antiviral drugs, which could also be used for inhibit other cytoplasmic replication viruses.