MedChem-antiviralagents2006课件.ppt

Viruses Size: 0.02 ~ 0.4 mm Consist of a nucleic acid core --- DNA --- RNA Capsid（病毒壳体）+ Protein Coat --- Nucleocapsid Envelope composed of glycoproteins that are viral antigens Complete package is known as VIRION 病毒感染 急性感染：流感，甲肝，非典； 慢性感染：乙肝，可携带很长一段时间，然后变成活动性肝炎； 潜伏感染：疱疹病毒，巨细胞病毒，潜伏在人体内，在人体抵抗力下降时出现症状； 慢病毒感染：HIV-1，在感染人体后3-10年后才发病； 机会性感染：病毒在人体内存在，但通常不致病，但在免疫力下降时出现症状。 病毒感染具有高传染性和引发其它疾病的危险。 病毒感染不一定发病，与免疫学因素和遗传因素有关。 抗病毒感染和药物治疗 20世纪在疾病的治疗方面取得了划时代的进步，尤其是化学疗法的发明，使许多传染病得到有效控制。1910年欧利希与秦佐八郎研制成抗梅毒药物606，开创了化学疗法；抗生素的应用无疑是化学治疗学的里程碑。 与抗菌药相比，抗病毒药发展缓慢。一方面是因为病毒整合到细胞里面，合二为一，很难区分，另一方面是很多病毒缺乏细胞或动物模型。 疫苗是控制病毒性疾病的理想手段，但由于许多病毒容易变异、亚型很多、而且缺乏细胞模型，因此抗病毒药物一直是病毒性疾病控制的主要手段。 Antiviral Agents Concept --- Selective toxicity --- Broad-spectrum activity --- Inhibit viral replication --- Reach target organ without interfering with the immunity of the individual Control of Virally-Transmitted Diseases Immunization: Active or passive, protects from disease, but does not treat existing disease; Interferons: Recombinant versions of naturally occurring immune modulators are available; Synthetic antiviral agents: Directed at any phase of viral reproduction. Rational Approaches in the Design of Antiviral Agents Modification of existing antiviral agents. Better oral bioavailability, better CNS bioavailability, lesser side effects, more potent antiviral effect, less likelihood of developing resistance. Purposefully designed antiviral agents New synthetic compounds are purposefully synthesized with the view of inhibiting one or more specific steps in viral replication. Viruses commandeer mammalian cells to produce new viruses Early phases of viral reproduction: Attachment to specific sites on target cell; Entry, uncoating of viral genetic material in cell; Transcription of viral genome to new proviral DNA. Late phases of viral reproduction: Transcription of proviral DNA to viral mRNA, genome; Translation of viral mRNA to viral precursor proteins; Processing precursors to mature protein products. Assem