Control of Virus Infections- Antivirals

Question 1

What are the phases of the influenza virus?

Answer 1

Phase 1- animal to animal transmission
Phase 2- an animal influenza virus is capable of human infection
Phase 3- small outbreaks among close populations but not through human to human contact
Phase 4 - human to human transmission
Phase 5 - spread across two countries or more in one of the WHO regions
Phase 6- spread across two countries or more in one of the WHO regions plus spread to another WHO region

Question 2

What are examples of antiviral drugs for influenza?

Answer 2

Anti-influenza drugs: Amantadine

• Interacts with influenza viral M2 protein (ion channel)
• Blocks entry of protons into virions, prevents uncoating
- Prevents low pH

Zanamivir and Oseltamivir

• Inhibitors designed to mimic natural ligand, sialic acid
• Affect the action of NA in cleaving sialic to release new infectious particles
• Closer inhibitors to natural compound, less likely target can change to avoid binding drug while maintaining viable function
• Target the exit or maturation phase
• The more you make the drug like the natural product, the lower the likelihood of mutation
• Due to the error prone nature of the viral RdRp mutations can frequently occur that confer resistance to antivirals - especially if the antivirals are excessively used
Circulating H1N1 and H3N2 viruses are now largely resistant to Adamantanes, not recommended for use

Question 3

What are some antiviral drugs for HIV?

Answer 3

Antiviral drugs: HIV protease inhibitors

• The HIV protease is absolutely required for production of infectious virions
• It is present in the virion and becomes activated upon final assembly and exit of the virion
• It cleaves the Gag-Pol polyprotein into the final products:
  
  • Capsid, matrix, nucleocapsid, reverse transcriptase, integrase and protease

• Blocking the function of the protease will stop the released virus from becoming infectious
They bind in the enzyme active site and block its activity

Question 4

What is HAART?

Answer 4

Highly active antiretroviral therapy

- Combination of several (typically three or four) antiretroviral drugs

Question 5

What are nucleoside analogues? What do they target?

Answer 5

• Acyclovir for Herpesvirus infections
• How does it work?
• What determines its specificity for the virus?
• Acyclovir is a guanosine analogue
• Phosphate groups can be added so that the analogue can be incorporated into DNA
• But the 3’ hydroxyl group required to extend the DNA polymer is absent
• Acyclovir is a prodrug: it must first be activated by the viral TK to subsequently be processed by cellular enzymes
The final product Acyclovir-TP is incorporated into DNA and will cause chain termination and the infected cell will die

Question 6

Antivirals against HCV- Hepatitis C

Answer 6

• Hepatitis C is a liver disease: the virus HCV can cause both acute and chronic hepatitis infection,
  
  • Ranges in severity from a mild illness lasting a few weeks to a serious, lifelong illness
• HCV is a bloodborne virus
• 130-150 million people globally have chronic hepatitis C infection
• A significant number of those who are chronically infected will develop cirrhosis or cancer
• 350,000 to 500,000 people die each year from hepatitis C related liver diseases
• Antiviral medicines can cure hepatitis C infection, but access to diagnosis and treatment is low
  
  • Quite expensive to treat ($90,000 per treatment)
• Antiviral treatment is successful in 50-90% of persons treated
  
  • Depending on the treatment used
  • Shown to reduce the development of liver cancer and cirrhosis
• There is currently no vaccine for HCV

Question 7

What are DAA?

Answer 7

Direct-acting antivirals

- The patient may be cured of HCV, however the infection is still not prevented - patients can be reinfected