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Antiretroviral targets in the viral life cycle Viral Replication and Drug targets.

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Presentation on theme: "Antiretroviral targets in the viral life cycle Viral Replication and Drug targets."— Presentation transcript:

1 Antiretroviral targets in the viral life cycle Viral Replication and Drug targets

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3 Available Antiretroviral Agents Nucleoside RTIs Zidovudine (ZDV) Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Lamivudine (3TC) Abacavir (ABC) Emtricitabine (FTC) Nonnucleos(t)ide RTIs Nevirapine (NVP) Delavirdine (DLV) Efavirenz (EFV) Etravirine (ETR) Tenofovir DF (TDF) Protease Inhibitors Saquinavir (SQV) Ritonavir (RTV) Indinavir (IDV) Nelfinavir (NFV) Amprenavir (APV) Lopinavir/r (LPV/r) Atazanavir (ATV) Fosamprenavir (Fos-APV) Tipranavir (TPV) Darunavir (DRV) Boosters Ritonavir (RTV) Cobicistat* (cobi) Fusion Inhibitor Enfuvirtide (T-20) CCR5 Antagonist Maraviroc (MVC) Integrase Inhibitors Raltegravir (RAL) Dolutegravir* Elvitegravir* * In expanded access or submitted for regulatory approval

4 Add HAART Remove HAART Effect of Cessation of Therapy On Viral Load Limit of Detection Viremia Years

5 Stevenson, M. Nature Med 9:853-860, 2003

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7 gp120 p24 Viral RNA RT & other virion proteins CD4 CXCR4 Binding HIV Lifecycle: A.Entry Inhibitors: CCR5 antagonist, maraviroc CCR5

8 gp120 p24 Viral RNA RT & other virion proteins Fusion & uncoating HIV Lifecycle: B.Fusion Inhibitors: T20

9 gp120 p24 Viral RNA RT & other virion proteins Reverse transcription HIV Lifecycle: C. Reverse Transcriptase (RT) Inhibitors: 1. Nucleoside RT inhibitors (NRTIs) 2. Non-Nucleoside RT Inhibitors NNRTIs)

10 gp120 p24 Viral RNA RT & other virion proteins Nuclear localization & entry HIV Lifecycle:

11 gp120 p24 Viral RNA RT & other virion proteins HIV Lifecycle: Integration D.Integrase Inhibitors: raltegravir

12 gp120 p24 Viral RNA RT & other virion proteins Integrated provirus HIV Lifecycle:

13 gp120 p24 Viral RNA RT & other virion proteins Viral Gene Transcription HIV Lifecycle:

14 gp120 p24 Viral RNA RT & other virion proteins Translation HIV Lifecycle:

15 gp120 p24 Viral RNA RT & other virion proteins Post-translational processing HIV Lifecycle:

16 gp120 p24 Viral RNA RT & other virion proteins Assembly HIV Lifecycle:

17 gp120 p24 Viral RNA RT & other virion proteins Budding HIV Lifecycle: E. Protease Inhibitors: e.g. Lopinavir, Indinavir Inhibition of Virion Maturation

18 CD4 CXCR4 Binding Fusion & Entry Nuclear localization & entry Reverse transcription Integration Infection gp120 p24 Viral RNA RT & other virion proteins

19 Expression gp120 p24 Viral RNA RT & other virion prteins Budding Assembly Viral Gene Transcription Translation Post-translational processing

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