D.5 Anti-viral medications

Viruses

• Antibiotics are very effective against bacteria, however they are ineffective against viruses, which differ from bacteria
  • Bacteria are living cells which feed, excrete grow and multiply
  • Viruses lack cellular structure and do not have their own metabolism. This makes it more difficult to actually target
• Viruses are not considered life forms but complex chemical compounds which can by synthesized in the lab
• The structure of virus is a protein containing the genetic material of the virus (RNA or DNA) on the inside
• Viruses exist outside living organisms, but they cannot perform any biological functions on their own, they act as parasites using the metabolism of host cells to create copies of themselves
• They do this by injecting their genetic material into the cell, the cell interprets it as instructions for a new protein, however it ends up making another virus. The viruses eventually break free from the cell destroying it in the process
• Most viral diseases have no cure and can only be treated by reducing pain/fever. Example of major virus outbreak was smallpox and was cured by use of vaccinations which is a form of prevention

Antiviral drugs

• Antivirals do not specifically “kill” the viruses because they are not living, but they do interfere with different stages in their replication cycle including
  • Attachment to host cell
    • Antivirals bind to cell receptors preventing attachment of viruses. Slow and expensive process, no commercial products
  • Uncoating of virus and injection of viral DNA into cell
    • Antivirals inhibit uncoating of virus and injection of genetic material. This strategy was utilized by amantadine and rimantadine, drugs for influenza and common cold. However, all viruses have now developed resistance
  • Biosynthesis of viral components
    • Antivirals mimic the structures of nucleotides which prevent biosynthesis of these components. Drugs include acyclovir and zidovudine which are effective against herpes and HIV
  • Release of viruses from the cell
    • Drugs oseltamivir (Tamiflu) and Zanamivir (Relenza), prevent the release of virus copies from the cell inhibiting certain viral enzymes called neuraminidases. This inhibition keeps viruses trapped in host cell preventing spread around the body
    • Both oseltamivir and zanavir are very similar in structure. They both contain a six membered ring with three chiral carbons. However they have different side chains containing different functional groups ultimately affecting the properties of these drugs.
    • Oseltamivir is inactive in original form due to ester group. In water, this is hydrolyzed into a carboxyl group producing active metabolite with enhanced antiviral activity

HIV and AIDS

• The virus, human immunodeficiency virus (HIV), is responsible for acquired immunodeficiency syndrome (AIDS), which is characterized by progressive failure of the immune system and development of life-threatening infections
• HIV is hard to treat because
  • Extremely fast at replication
  • Targets white blood cells which are in fact responsible for preventing attacks on the body
  • HIV is able to incorporate itself into host DNA where it can remain dormant for years
• HIV is an example of a retrovirus which uses reverse transcriptase to produce DNA strands from their RNA genomes.
• Since reverse transcriptase is used only by viruses, its inhibition does not affect normal cells
• The antiviral drug called zidovudine uses this technique to combat AIDS and prevent HIV transmission
• However, zidovudine does not eliminate HIV completely, allowing virus to become resistant over time
• Thus, zidovudine is used in combination with other inhibitors to effectively target viruses
• Lack of treatment of AIDS is complicated by health care, poor education and sociocultural issues. Anti-retroviral treatment costs more than average income in some countries, so it is unaffordable. This results in many people spreading the disease unknowingly.
• Increase drug use, prostitution, lack of condoms during sex increase risk of AIDS