Antiviral Agents.pptVIP

Antiviral Agents GAO Fen-Fei Overview Viruses are obligate intracellular parasites; their replication depends primarily on synthetic processes of the host cell. Antiviral agents must either block viral entry into or exit from the cell or be active inside the host cell. Research in Antiviral Chemotherapy In the early 1950s, IdUR and Trifluorothymidine(三氟胸腺嘧啶核苷) In the mid 1970s, Adenine arabinoside (Vidarabine,ara-A,阿糖腺苷) In the late 1970s, Acyclovir (阿昔洛韦) With the appearance of AIDS epidemic in the 1990s, Inhibitor reverse transcriptase or the protease Antiretroviral (Anti-HIV) Agents The first available agents: Nucleoside analog class → competitive inhibition of the viral reverse transcriptase Nonnucleoside reverse transcriptase inhibitors The protease inhibitors The combination of at least two antiretroviral agents (cocktail therapy) → enhancing potency and delaying resistance Nucleoside Reverse Transcriptase Inhibitors Derivatives of Pyramine: AZT, ddC, d4T, 3TC Derivatives of Purine: ddI, ABC Mechanism of Action Competitive inhibition of HIV-1 reverse transcriptase; Incorporated into the growing viral DNA chain → cause termination Drugs requires intracytoplasmic activation--- phosphorylation → triphosphate form Most have activity against HIV-2 as well as HIV-1. Zidovudine Azidothymidine (叠氮胸腺嘧啶), AZT Deoxythymidine analog anti-HIV-1 and HIV-2 Well absorbed from the gut and distributed to most body tissues and fluids, including the cerebrospinal fluid. Eliminated primarily by renal excretion following glucuronidation in the liver. Decrease the rate of clinical disease progression and prolong survival. Treatment HIV-associated dementia(痴呆) and thrombocytopenia(血小板减少). Reduce the rate of vertical (mother-to-newborn) transmission of HIV. Adverse effect: myelosuppression(骨髓抑制) → anemia or neutropenia; gastrointestinal intolerance, headachs, insomnia(失眠) Zalcitabine (ddC) Cytosine analog Anti-HIV-1 Zalcitabine + Zidovudine + one protease inhibitor Long intracellu