HIV的繁殖过程大致分为以下几个步骤：吸附、侵入和脱壳、逆转录、整合、病毒RNA和蛋白质的合成、装配、释放和成熟，每个环节均可作为筛选HIV药物的靶点，其中蛋白质的合成和病毒基因组核酸复制是最关键的步骤。筛选HIV药物的焦点就是寻找这些特异性酶的抑制剂。根据抑制剂的作用机理可将它们分为两类：①核苷类逆转录酶抑制剂，如AZT、ddI、ddC、d4T、3TC等；②非核苷类逆转录酶抑制剂，如Nevirapine、Delavirdine等。拉米夫定(3TC)的发现及广泛应用，极大地促进了L-核苷类抗病毒化合物的研究，如L-FTC、L-FMAU等，实验证明，有些化合物抗病毒生物活性比其相应的D-型异构体要强，而药物的毒副作用则远低于其相应的D-型异构体，为此我们合成了一系列D-及L-型核苷类化合物。迄今尚未见到本发明之含2’-氟-4’-取代D-和L-核苷类似物的文献报道，以及将其用于制备抗病毒的药物。所合成化合物的抗病毒活性实验结果表明有些化合物的抗HIV活性大于AZT，抗HBV活性大于3TC。对此已申请中国发明专利3项，授权1项，申请PCT专利1项，发表相关学术论文9篇，完成了研究计划内容。

HIV proliferation process can be divided into the following steps: adsorption, invasion and shelling, reverse transcription, integration and synthesis, assembly, release and mature of viral RNA and protein, each of which can be used as screening targets for HIV drugs, including protein synthesis and viral genomic DNA replication, the most critical steps. Currently screening of anti-HIV drugs is focused on identification of those specific enzyme inhibitors, including reverse transcriptase (RT) inhibitors, protein synthesis inhibitors and reverse transcriptase initiation inhibitors. According to the mechanism of inhibitors, these agents could be divided into two categories: 1) nucleoside reverse transcriptase inhibitors, including zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), Stavudine set (d4T), lamivudine (3TC), Abacavir (Abacavir); 2) non-nucleoside reverse transcriptase inhibitors, existing drugs including nevirapine (Nevirapine), Delavirdine and Efavirenz. The invention and wide use of lamivudine (3TC) accelerated the study in L-nucleosides antivirus analogs, such as L-FTC, L-FMAU. The antivirus activity of some L-nucleosides was more effective than it’s D-isomers, and the toxicity was less at the same time. So a series of D- and L-nucleosides were synthesized. According to the present literature, however, there are no relevant reports about the compounds containing 2'- fluoro - 4' - substituted-D-and L-nucleoside analogues in our invention as well as their application in preparation of compositions against HIV, HBV and HCV. The results of antivirus activity experiments showed some compounds’ anti-HIV activity was more effective than AZT and anti-HBV activity more effective than 3TC. Based on the research program above, we have applied three Chinese patents and one PCT patent, and one Chinese patent was authorized, and 9 papers were published.

HIV的繁殖过程大致分为以下几个步骤：吸附、侵入和脱壳、逆转录、整合、病毒RNA和蛋白质的合成、装配、释放和成熟，每个环节均可作为筛选HIV药物的靶点，其中蛋白质的合成和病毒基因组核酸复制是最关键的步骤。筛选HIV药物的焦点就是寻找这些特异性酶的抑制剂。根据抑制剂的作用机理可将它们分为两类：①核苷类逆转录酶抑制剂，如AZT、ddI、ddC、d4T、3TC等；②非核苷类逆转录酶抑制剂，如Nevirapine、Delavirdine等。拉米夫定(3TC)的发现及广泛应用，极大地促进了L-核苷类抗病毒化合物的研究，如L-FTC、L-FMAU等，实验证明，有些化合物抗病毒生物活性比其相应的D-型异构体要强，而药物的毒副作用则远低于其相应的D-型异构体，为此我们合成了一系列D-及L-型核苷类化合物。迄今尚未见到本发明之含2’-氟-4’-取代D-和L-核苷类似物的文献报道，以及将其用于制备抗病毒的药物。所合成化合物的抗病毒活性实验结果表明有些化合物的抗HIV活性大于AZT，抗HBV活性大于3TC。对此已申请中国发明专利3项，授权1项，申请PCT专利1项，发表相关学术论文9篇，完成了研究计划内容。