Mechanisms of Antivirals

Question 1

What are the uses of anti-virals ?

Answer 1

To treat acute infections
Treatment of chronic infection
Post-exposure prophylaxis and preventing infection

Pre-exposure prophylaxis
Prophylaxis for reactivated infection

Question 2

What is selective toxicity?

Answer 2

The toxin should be selective for the virus only and not for humans

Due to differences in structure and metabolic pathways between host and pathogen

Harm micro-organisms not the host

Target in microbe not host

There are variations between microbes and their resistance to antivirals

Question 3

Why is it difficult to develop effective non-toxic anti-viral drugs ?

Answer 3

Viruses enter cells using cellular receptors which can have other functions

Viruses must replicate inside cells -obligate intracellular parasites

Virues take over the host cell replicative machinery

Some viruses have high mutation rates = Quasispecies (have large numbers of variant genomes due to mutations)

Anti-viral must be selective in their toxicity
exert their action only on infected cells

Some viruses are able to remain latent
for.eg herpes can remain latent in basal ganglia

Some viruses are able to integrate their genetic material into host cells

cannot find a drug to selectively remove this DNA

Question 4

Outline the general viral life cycle

Answer 4

1. The virus is recognised by a cell surface receptor
2. Attaches and becomes internalised via endocytosis or membrane fusion on the side .
3. Uncoating of the virus particle and release of its genome into the cytoplasm
4. Genome replication /transcription to create viral messenger RNA
5. This viral mRNA will then migrate to the endoplasmic reticulum where it is translated to make virally directed virus proteins.
6. There is assembly of virus which is the genome + viral proteins which are packaged into viral particles
7. The viruses leave cell through budding in membrane or lysis and release.

Question 5

What are some modes of action of selected anti-virals ?

Answer 5

Preventing virus adsorption onto host cell
Preventing penetration
Preventing viral nucleic acid replication (nucleoside analogues)
Preventing maturation of virus (reassembly of virus and lytic release)
Preventing virus release
Prevents uncoating
-When virus enters the cell , it will fuse its membrane with the dosome membrane to prevent uncoating

Question 6

What are some examples of selective toxicity viral targets?

Answer 6

Thymidine kinase 
Protease in HIV 
Reverse transcriptase of HIV 
Viral DNA polymerases 
Neuraminidiase of influenza

These can act as selective targets with minimal effect on host enzymes

Question 7

Give an example of a virus which can cause muco-cutaneous lesions

Answer 7

muco-cutaneous lesions are sores of the skin and mucous membrane.

This can be caused by human herpes simplex type 1 which can also cause genital herpes.

Varicella zoster virus (chicken pox)
Cytomegalovirus
Epstein-Barr virus

Question 8

What are some examples of herpes viruses and what antivirals can be used to treat them ?

Answer 8

Herpes simplex
Varicella zoster virus (chicken pox)
Cytomegalovirus
Epstein-Barr virus 
Acyclovir
 IV/oral//topical
 For HSV,VZV treatment/prophylaxis
 Good at CMV/EBV prophylaxis but not as a treatment
 Low toxicity
 Ganciclovir
 IV/oral
 For CMV
 Forcarnet
 IV/local application
 For CMV
 Cidofovir
 IV
 For CMV

Question 9

How does acyclovir work and how does it use selective toxicity ?

Answer 9

CHECK DOCUMENT

Question 10

Why is aciclovir safe and effective ?

Answer 10

CHECK DOCUMENT