Mechanisms of Anti-Virals Flashcards
What are the two antimicrobial agents?
β Antibiotics target bacteria
β Antivirals target viruses
Why do we need antivirals?
β for quick killer viruses
β slow progressive chronic diseases
What are the slow progressive viruses that lead to cancer?
β Hep B
β Hep C
β HPV
β HIV
What are the 5 uses of antivirals?
β Treatment of acute infection β Treatment of chronic infection β Post-exposure prophylaxis β Pre-exposure prophylaxis β Prophylaxis for reactivated infection
What are three viruses causing acute infection that antivirals can be used for?
β Influenza
β Chickenpox
β Herpes
What are three viruses that cause chronic infection that antivirals can be used for?
β HCV
β HBV
β HIV
When do you use antivirals prophylactically?
β post exposure HIV
β pre exposure HIV
When do you use antivirals prophylactically for a reactivated infection?
β transplantation
β CMV
Why does selective toxicity work?
β Due to differences in the structure and metabolic pathways between the host and the pathogen
Where should the target for selective toxicity ideally be?
β inside the pathogen
What are the 6 reasons that it is so difficult to develop effective and non-toxic antiviral drugs?
1) Viruses enter cells using cellular receptors which may have other function
2)Viruses must replicate inside cells - obligate intracellular parasites
3)Viruses take over the host cell replicative machinery
4)Viruses have a high mutation rate - quasispecies
5)Antivirals must be selective in their toxicity
I.e exert their actions only on infected cells
6)Some viruses are able to remain in a latent state e.g Herpes, HPV
7)Some viruses are able to integrate their genetic material into host cells e.g HIV
Why is it difficult to make drugs that target fungi and parasites?
β They are eukaryotic organisms
β the targets for the drugs are similar to the host
What happens if you block viral enzymes?
β viral enzymes may be similar to host enzymes
β it may kill the cell
What happens if you block cellular virus receptors?
β It may have an important function and kill the cell
Describe the virus life cycle in 5 steps?
1) Virus attaches to the membrane
2) It enters via membrane fusion or endocytosis
3) When the virus is inside it uncoats and releases the genome
4) The genome replicates itself
5) the virus reassembles and escapes
What are the two ways that a virus can escape the cell?
β Virus reassembles either by budding through the membrane
β Viruses assemble inside the cell and escape by cell lysis
What are the 5 ways in which antivirals work?
β Prevent virus adsorption onto the host cell
β Preventing penetration
β Preventing viral nucleic acid replication (nucleoside analogues)
β Preventing maturation of virus
β Preventing virus release
What was amantadine used to treat?
βInfluenza A
What drugs inhibit nucleic acid polymerisation?
β Acyclovir
β Ganciclovir
β Ribavirin
How do acyclovir and ganciclovir work?
β They inhibit nucleic acid polymerisation by targeting reverse transcriptase or DNA polymerase
How does ribavirin work?
β analogue of GTP
β Compromises the genome replication of the virus
How does Zanamivir work?
β Blocks the release of the virus from the cell
What do protease inhibitors do?
β block particle maturation and assembly of the virus
What are 5 examples of viral targets?
β Thymidine kinase : HSV/VZV/CMV β Protease of HIV β Reverse transcriptase of HIV β DNA polymerases β Neuraminidase of influenza virus
What are 4 examples of human herpesviruses?
β HSV
β VZV
β CMV
β EBV
What are the methods of administration of Aciclovir?
β IV
β oral
β topical
What is Aciclovir used to treat?
β HIV/VZV treatment/prophylaxis
β CMV/EBV prophylaxis
What are the methods of administration of Ganciclovir and what is it used to treat?
β IV/oral
β CMV
What are the methods of administration of Foscarnet and what is it used to treat?
β IV/oral
β CMV
What is the method of administration of Cidofovir and what is it used to treat?
β IV
β CMV
Describe the mechanism of action of Aciclovir
1) When GTP is incorporated into DNA you need a 3β OH group but the aciclovir does not have it
2) It is a chain terminator
3) ACV is first phosphorylated by a viral thymidine kinase (encoded by viral genome)
4) Once the ACV is phosphorylated it remains stable but then it is di and tri phosphorylated by cellular components
5) When it is triphosphorylated it becomes active
6) It then becomes a competitive inhibitor for viral DNA polymerase
7) It competes with normal GTP and stop the viral polymerase from synthesizing the viral genome
What is Aciclovir?
βGTP analog that has lost some ribose sugars
What are the two reasons that Aciclovir has been given selective toxicity?
1) It is selectively activated only inside infected cells because it is activated by a viral thymidine kinase
2) Selective inhibition of DNA polymerase mainly targeting the viral DNA polymerase
Why does aciclovir not affect cellular phosphokinases?
β HSV thymidine kinase has 100x the affinity for aciclovir compared to cellular ones
Why does aciclovir not affect DNA polymerase?
β Aciclovir triphosphate has 30x the affinity for HSV DNA polymerase compared to cellular DNA polymerase
Why is aciclovir so effective?
β It is a highly polar compound
β Difficult to leave or enter cells
What is Aciclovir used for in the treatment of Herpes virus?
β Treatment of encephalitis
β Treatment of genital infection
β Suppressive therapy for recurrent genital herpes
What is Aciclovir used for in the treatment of VZV?
β Treatment of chickenpox
β Treatment of shingles
β prophylaxis of chicken pox
