Control of Virus Infections- Antivirals Flashcards Preview

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Flashcards in Control of Virus Infections- Antivirals Deck (7)
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1
Q

What are the phases of the influenza virus?

A

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

2
Q

What are examples of antiviral drugs for influenza?

A

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

3
Q

What are some antiviral drugs for HIV?

A

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

4
Q

What is HAART?

A

Highly active antiretroviral therapy

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

5
Q

What are nucleoside analogues? What do they target?

A

• 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

6
Q

Antivirals against HCV- Hepatitis C

A
  • 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
7
Q

What are DAA?

A

Direct-acting antivirals

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