Mechanisms of Antivirals Flashcards
What are the uses of anti-virals ?
To treat acute infections
Treatment of chronic infection
Post-exposure prophylaxis and preventing infection
Pre-exposure prophylaxis
Prophylaxis for reactivated infection
What is selective toxicity?
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
Why is it difficult to develop effective non-toxic anti-viral drugs ?
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
Outline the general viral life cycle
- The virus is recognised by a cell surface receptor
- Attaches and becomes internalised via endocytosis or membrane fusion on the side .
- Uncoating of the virus particle and release of its genome into the cytoplasm
- Genome replication /transcription to create viral messenger RNA
- This viral mRNA will then migrate to the endoplasmic reticulum where it is translated to make virally directed virus proteins.
- There is assembly of virus which is the genome + viral proteins which are packaged into viral particles
- The viruses leave cell through budding in membrane or lysis and release.
What are some modes of action of selected anti-virals ?
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
What are some examples of selective toxicity viral targets?
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
Give an example of a virus which can cause muco-cutaneous lesions
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
What are some examples of herpes viruses and what antivirals can be used to treat them ?
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
How does acyclovir work and how does it use selective toxicity ?
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Why is aciclovir safe and effective ?
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