antiviral

Antiviral Medications Overview
  • Outline
    • Introduction to viruses (Classification and Definitions)
    • Prevention and Therapies
    • Antivirals for herpes simplex
    • Antivirals for influenza
    • Antivirals for HIV
Lecture Objectives
  • Define key terms:
    • Virulence: Degree of pathogenicity of a virus.
    • Pathogenicity: Ability to cause disease.
    • Viral Range: Types of cells or species a virus can infect.
    • Carriers: Individuals who harbor the virus without showing symptoms, serving as reservoirs.
    • Latency: Dormancy period of a virus within a host.
  • Describe the structure of a virion:
    • Consists of nucleic acid (DNA/RNA) and a protein coat (capsid).
    • Some have a lipid envelope.
  • Outline the lytic cycle of a virus:
    • Processes: absorption, penetration, replication, release
  • Classify viral classes and distinguish features.
  • Describe types of antivirals and mechanisms of action.
Virology Basics
  • Viruses:
    • Obligate intracellular parasites relying on the host's machinery for reproduction.
    • Exist as independent particles (virions) outside host cells.
  • Virion Structure:
    • Composed of:
    • Double or single stranded DNA or RNA.
    • Protein coat (capsid).
    • Sometimes a lipid envelope from the host cell containing antigenic glycoproteins.
  • Sizes:
    • Viruses are significantly smaller (~1/100th the size of average bacteria).
Viral Classification
  • Viral Range:
    • Group of cell types or species a virus can infect.
  • Bacteriophage: Virus that infects bacteria.
  • Animal/Plant Viruses: Specific to a type of host, limited cross-phyla infection.
Virus Shapes
  • Classification by shape of capsid:
    • Helical: e.g., Tobacco mosaic virus, Rabies virus.
    • Icosahedral: e.g., Poliovirus, Herpes simplex virus.
    • Complex: e.g., Smallpox virus.
Viral Pathogenicity and Lifecycle
  • Pathogenicity: Ability of viruses to cause disease.
  • Virulence: Measure of pathogenicity.
  • Life Cycle Stages:
    • Absorption → Penetration → Replication → Release
    • Initial interaction between viral proteins and host cell receptors determines host range.
    • Viral DNA/RNA enters host cell, utilizing host's machinery to replicate.
Central Dogma of Biology
  • Process:
    • DNA → mRNA → Proteins
    • DNA Replication and Transcription occur in the nucleus; Translation occurs in the cytoplasm.
Virus Types: RNA and DNA

  • DNA Viruses:

    • Enter nucleus, integrated into host genome, transcribed by host polymerase.
    • Poxviruses: Exception, replicate in cytoplasm using their own polymerase.

  • RNA Viruses:

    • Includes double stranded and single stranded types.
    • Most undergo replication in the cytoplasm.
Retroviruses
  • Contain RNA genome that converts to DNA in host (via reverse transcriptase).
  • Integration into host genome leads to continuous replication without immediate lysis.
Vaccination Strategies
  • Vaccination is a cost-effective preventive measure against viral infections.
  • Types of vaccines include:
    • Live-attenuated
    • Killed viruses
    • Viral proteins or mRNA (antigens).
Antiviral Therapies
  • Mechanisms:
    • Target various stages of replication: entry, nucleic acid/protein synthesis, and release.
    • Combination therapies enhance effectiveness and delay resistance emergence.
    • Drugs are generally virustatic, affecting only replicating viruses.
Antivirals for Herpes Simplex
  • Acyclovir: Nucleoside analog.
    • Incorporates into viral DNA, lacking functional groups leading to chain termination.
    • Requires phosphorylation to active form; selective toxicity as viral thymidine kinase phosphorylates it more effectively than mammalian enzymes.
  • Resistance Mechanisms:
    • Impaired thymidine kinase production or substitutions in viral DNA polymerase.
Antivirals for HIV
  • HIV: Lentivirus that infects CD4+ T-cells, leading to AIDS.
  • Antiretroviral drugs target different stages of HIV life cycle:
    • Entry Inhibitors: Block fusion and entry into T-cells. E.g., Maraviroc.
    • NRTIs: Block reverse transcription by mimicking nucleosides, leading to chain termination.
    • Integrase Inhibitors: E.g., Raltegravir, block insertion into host DNA.
    • Protease Inhibitors: Target viral protease for assembly of virions.
Antivirals for Influenza
  • Amantadine: Inhibits viral uncoating for Influenza A.
    • Effectiveness decreasing due to emerging resistant strains.
    • Prophylactic use and wartime measures against failure of vaccination in high-risk groups.
  • Zanamivir: Inhibits neuraminidase, preventing viral release and spread.