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上海交通大学:《药理学 Pharmacology》课程教学资源(讲义课件)Antiviral drugs(抗病毒药)

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上游克通大¥ Shanghai Jiao Tong Univer Antiviral drugs (抗病毒药) 2012.12

Antiviral drugs (抗病毒药) 2012.12

上降充通大学 Shanghai Jiao Tong University 9p120 Docking Glycoprotein Lipid RNA Membrane 9p41- Transmembrane Capsid Glycoprotein Matrix Reverse Transcriptase HIV

Shanghai Jiao Tong University HIV

上游充通大学 Shanghai Jiao Tong University gp120 gp41 viral envelope p17 W0000000000o0000 p24 000000000000 protease reverse transcriptase RNA Human Immunodeficiency 000 Virus-Structure

Shanghai Jiao Tong University

上商充通大¥ Shanghai Jiao Tong University Virus Structure Surface proteins Nucleocapsid Protein shell Nucleic acid Nucleic acid. Lipid layer Membrane (matrix protein) (a) (b) .Virus contains a few proteins,lipids and nucleic acid which are accurately replicated by the infected cell to produce more viruses

Shanghai Jiao Tong University Virus Structure Virus Structure •Virus contains a few proteins, lipids and nucleic acid which are accurately replicated by the infected cell to produce more viruses

上浒文通大学 Virus-induced diseases Shanghai Jiao Tong University Hepatitis (type A,B,C,...) Influenza AIDS Herpes(疱疹) Infantile cytomegalovirus(CMV,巨细胞病毒) infection (one of the causes of congenital rubella- induced deformity) Rotavirus(RotV轮状病毒),diarrhea 国 Mumps virus induced orchitis(腮腺炎) (15%一25 %)sterility

Shanghai Jiao Tong University Virus-induced diseases Hepatitis (type A, B, C, …) Influenza AIDS Herpes(疱疹) Infantile cytomegalovirus (CMV,巨细胞病毒) infection (one of the causes of congenital rubella￾induced deformity) Rotavirus (RotV轮状病毒), diarrhea Mumps virus induced orchitis(腮腺炎) (15%-25 %),sterility …

Binding of the virus to the HIV life cycle Shang T-cell through the gp120 Breakdown of the and CD4 receptors polyprotein precursor by the protease to give structural proteins and Fusion through viral gp41 enzymes and loss of its envelope, 酶后期修饰 被PIs抑制 the uncoating Migration of viral RNA to 细胞内 the cytoplasm as mRNA Viral DNA formation by to encode the synthesis reverse transcriptase of viral proteins followed by RNase 病毒mRNA Splicing of viral RNA >7 Viral DNA entry to the by host RNA host cell nucleus through polymerase to 逆转录 produce viral mRNA 编码RNA its nuclear pores 被 8神制 细胞核 病毒RNA 转录

Shanghai Jiao Tong University HIV life cycle 结合 细胞外 HIV蛋白酶后期修饰 被PIs抑制 细胞膜 装配 病毒蛋白 双链DNA 细胞内 翻译 病毒mRNA 编码RNA 病毒RNA 转录 整合 脱壳 细胞核 逆转录 编码RNA 被 抑 制 R T I s Fusion through viral gp41 and loss of its envelope, the uncoating Viral DNA formation by reverse transcriptase followed by RNase Viral DNA entry to the host cell nucleus through its nuclear pores Splicing of viral RNA by host RNA polymerase to produce viral mRNA Migration of viral RNA to the cytoplasm as mRNA to encode the synthesis of viral proteins Breakdown of the polyprotein precursor by the protease to give structural proteins and enzymes Binding of the virus to the T-cell through the gp120 and CD4 receptors

上游充更大睾 Host cell Cell membrane 2 00 Virus Ribosomes 6 and mRNA Chromosomes Host nucleus Sites of drug action 1.Attachment to host cell 3.Control of DNA,RNA,and/or 5.Assembly of virions 2.Uncoating of virus,and protein production 6.Release of virions entry of viral nucleic acid 4.Production of viral subunits into host cell nucleus (Modified from Brody TM,Larner J,Minneman KP:Human pharmacology:molecular to clinical,ed 3,St Louis,1998 Mosby) Fig.39-1.Virus replication.Some viruses integrate into host chromosome with development of latency

Shanghai Jiao Tong University

上浒文通大学 Viral replication Shanghai Jiao Tong University ①病毒识别并吸附到宿主细胞的表面; ②通过宿主细胞膜穿入易感细胞; ③脱壳; ④合成早期的调控蛋白及核酸多聚酶; ⑤病毒基因组(DNA或RNA)复制; ⑥合成后期的结构蛋白; ⑦子代病毒的组装: ⑧易感细胞释放子代病毒

Shanghai Jiao Tong University Viral replication ①病毒识别并吸附到宿主细胞的表面; ②通过宿主细胞膜穿入易感细胞; ③脱壳; ④合成早期的调控蛋白及核酸多聚酶; ⑤病毒基因组(DNA或RNA)复制; ⑥合成后期的结构蛋白; ⑦子代病毒的组装; ⑧易感细胞释放子代病毒

上浒充通大睾 Anti-viral attack steps Shanghai Jiao Tong University Single cell reproductive cycle of HAV receptor binding RNA uncoating translation and proteolytic processing Maturation and release RNA replication 4 R assembly and packaging

Shanghai Jiao Tong University Anti-viral attack steps

上克通大睾 Shanghai Jiao Tong University Viral entry and uncoating inhibitors 穿入和脱壳抑制剂

Shanghai Jiao Tong University Viral entry and uncoating inhibitors 穿入和脱壳抑制剂

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