Antiviral Drugs PDF

Antiviral Drugs Dr.Girish Meravanige College of Medicine, KFU Overview of Viral Infections  Learning objectives 1. Why is it so difficult to develop antiviral drugs? 2. Targets for Antiviral drugs ? 3. Basis of Antiviral therapy again...

Antiviral Drugs Dr.Girish Meravanige College of Medicine, KFU Overview of Viral Infections  Learning objectives 1. Why is it so difficult to develop antiviral drugs? 2. Targets for Antiviral drugs ? 3. Basis of Antiviral therapy against Herpes viruses ? 4. What is HAART with HIV infections? 5. Why does combination therapy work better with HIV infections than monotherapy? 6. What are Neuraminidase inhibitors that are used in Influenza infections? 7. What is the basis of Interferon therapy for Hepatitis C ?  Antiviral drugs Antiviral drugs are targeted towards viral encoded enzymes or structures of virus that are important for replication Antiviral drugs are available for viruses which cause significant morbidity and mortality It is difficult for the antiviral drugs to inhibit viral replication without harming the host cell Problems in developing Antiviral agents  Key is selectivity: - Structure of each virus differs - Periodic changes in the antigenic proteins of the virus (Mutation)  Toxicity: - Virus is an obligate intracellular parasite, it requires host cell functions for its infection, reproduction, and release (spread). Hence, antiviral agents must be able to inhibit the virus without seriously affecting the host cells.  Targets for Antiviral agents Structures/ Enzymes important for viral replication: DNA dependent DNA polymerase RNA dependent RNA polymerase RNA dependent DNA polymerase Integrase Protease Neuraminidase  Targets for Antiviral agents 1.Attachment and penetration of the virus into the host cell 2.Uncoating of virus (e.g., removal of the protein surface and release of the viral DNA or RNA) 3.Synthesis of new viral components by the host cell as directed by the virus DNA 4.Assembly of the components into new virus 5.Release of the virus from the host cell. HIV Virus structure  Antiretroviral drugs (ART) Nucleoside reverse transcriptase inhibitors: Zidovudine Non-Nucleoside reverse transcriptase inhibitors: Nevirapine Protease inhibitors: Indinavir Integrase inhibitors: Raltegravir Chemokine receptor antagonist: Maraviroc HIV fusion inhibitor: Enfuvirtide  HAART (Highly active antiretroviral therapy)  The standard HIV treatment consists of a combination of at least 3 drugs - 2 NRTIs with either a NNRTI or 1 or 2 PIs (often called “HAART”).  The goals of HAART: - To suppress HIV replication/viral load (< 50 copies/mL) as long as possible. - To reduce the likelihood of the virus developing resistance. - Restore/preserve immunologic function (CD4 count >200 cells/mm3) - To reduce mortality and morbidity rates among HIV-infected people. - To improve their quality of life. - Prevent HIV transmission  HAART As per WHO guidelines: A) Initiate ART if CD4 cell count ≤500 cells/ml. B) As a priority, initiate ART in all individuals with severe/advanced HIV disease (WHO clinical stage 3 or 4) or CD4 count ≤ 350 cells/cu mm C) Initiate ART regardless of WHO clinical stage or CD4 cell count in: Active TB disease HBV co-infection with severe chronic liver disease Pregnant and breastfeeding women with HIV  Herpes Simplex Viruses (HSV) HSV-1: Oral herpes HSV-2: Genital herpes  Antiviral therapy for Herpes viruses Acyclovir, Famciclovir : It competes with the Guanosine triphosphate to inhibit DNA polymerase Uses : Herpes simplex and varicella zoster  Anti Influenza drugs Neuraminidase inhibitor: (Uses: Influenza A&B) Oseltamivir, Zanamivir Amantadine and Rimantadine: Inhibits the uncoating & assembly of influenza A virus – Prevents viral replication (Used for only Influenza A)  Interferons Types: α, β, γ Mechanism of action: Inhibit viral replication by - Preventing the viral penetration - Viral assembly & release - Producing enzymes that inhibit the translation of viral mRNA into viral proteins Interferon-alpha 2b: Used in chronic hepatitis B & C infections Pegylated IFN-α 2a & 2b are superior to conventional IFN α 2a and 2b.