Mechanism of antivirals Flashcards
What are the uses of anti-virals?
- Treatment of acute infection
- Treatment of chronic infection
- Post-exposure prophylaxis(PEP) and preventing infection
- Pre-exposure prophylaxis(PrEP)
What is selective toxicity?
When a drug has a selective action against one component and not another
What is selective toxicity due to?
Due to the differences in structure and metabolic pathways between host and pathogen
What do antiviral harm?
Harm microorganisms, not the host
What should the target of the antiviral be?
We need for the target of the antiviral to be in the microbe, not in the host
Why is it difficult to make antivirals for viruses?
Difficult to make antivirals for viruses because viruses are intracellular organisms and use cellular machinery to replicate themselves,
Why is it difficult to make anti-fungal and anti-parasitic drugs?
Difficult to make antifungal and anti-parasitic drugs as well because they can be very similar to the host so hard to make something that only harms the microbe and not the host
Why is it difficult to develop effective, non-toxic antivirals?
- Viruses enter cells using cellular receptors which may have other functions
- Viruses must replicate inside cells – obligate intracellular parasites
- Viruses take over the host cell replicative machinery
- Viruses have high mutation rate - quasispecies
- Anti-virals must be selective in their toxicity
i. e. exert their action only on infected cells - Some viruses are able to remain in a latent state e.g. herpes, HPV
- Some viruses are able to integrate their genetic material into host cells
What is the life cycle of a virus?
- Virus enters and attaches to membrane
- Gets internalized by endocytosis or membrane fusion
- Once the virus is inside it has to uncoat and release its genome
- Genome replicates and makes mRNA
- mRNA goes to the ribosomes where it starts makes viral proteins
- Virus reassembles
- Virus can escape through cell lysis or budding and release
What do antiviral prevent?
- Preventing virus adsorption onto host cell
- Preventing penetration
- Preventing viral nucleic acid replication
- Preventing maturation of virus
- Preventing virus release
- Prevents uncoating
What do acyclovir, ganciclovir and ribavirin target?
Target reverse transcriptase’s or DNA polymerases
What is ribavirin and what does it compromise?
Ribavirin is a GTP analogue so compromises genome replication as it can’t make it’s genome because there are not enough precursors of like deoxy GTP
How does amantadine work and what does it prevent?
When virus enters the cell, it fuses its membrane with the liposome membrane from amantadine to prevent uncoating of the virus
What are examples of selective toxicity viral targets?
- Thymidine kinase
- Proteases from the genome of HIV
- Reverse transcriptase of HIV
- DNA polymerases
- Neuraminidase of influenza virus
What does herpes virus include?
- Herpes simplex (HSV),
- Varicella Zoster Virus (VZV)
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
What treatments are available for herpes?
- Acyclovir
- Ganciclovir
- Forcarnet
- Cidofovir
How is acyclovir administred?
IV/oral/topical
What is acyclovir for?
For HSV,VZV treatment/prophylaxis
What is acyclovir good at?
Good at CMV/EBV prophylaxis but not as a treatment
How is ganciclovir administred?
IV/Oral
What is ganciclovir for?
For CMV
How is forcarnet administred?
IV/local application
What is forcarnet for?
For CMV
How is cidofovir administred?
IV