Antivirals Flashcards
Viral replication is so intimately associated with the host cell that any drugs that interferes significantly with viral replication is …
likely to be toxic to the host
What is the most severe constraint limiting the use of antiviral drugs?
The toxicity to the mammalian cells, not the lack of efficacy
A successful antiviral drug should …
interfere with a virus-specfic function
either because the function is unique to the virus or the similar host function is much less susceptible to the drug
Aside from interfering with a virus specific function, what else can an antiviral do?
interfere with a cellular function necessary for viral replication
in this case, to be specific the antiviral drug must only affect virus infected cells - specificity could be obtained by restricting drug activation to virus-infected cells
What are the possible targets for antiviral therapy?
- prevention of entry into host cell
- Inhibition of virus uncoating
- integrase inhibitors
- duplication of the viral genome
- mRNA transcription and processing
- protein translation
- post-translational modification of proteins
- assembly of the components into the whole virus
How can we target/prevent the the virus from entering into host cells? (think HIV)
- inhibitors of attachment that compete with a viral receptor
- coreceptor antagonists
- fusion inhibitors that prevent fusion with host cells
What is maraviroc?
CCR5 coreceptor antagonist - used to prevent entry of HIV into host cells
should only be used in CCR5-trophic patients
How can HIV resist maraviroc?
by using the drug-bound form of CCR5 as a coreceptor — this is called noncompetitive resistance
What CYP is maraviroc metabolized by?
CYPA3
so adjust dose when used with drugs that inhibit or stimulated this enzyme to adjust for changes in metabolism
What is Enfuvirtide (T-20)?
a fusion inhibitor used for HIV because is specifically inhibits the function of gp41
it is derived from the natural gp41 HR2 sequence
When does viral uncoating occur?
at low pH at the level of endosomes or lysosomes (pH-dependent uncoating)
— note: this is different than fusions, which is pH-independent
What do integrase inhibitors do?
prevent the insertion of the virus genetic code into the DNA of infected cells by inhibiting the viral integrase
What class of drugs contain the best antiviral drugs available? Why?
Drugs that target duplication of the viral genome (aka polymerase inhibitors)
Drugs from this class are selective! b/c
- virus may used its own enzyme to activate the drug AND/OR
- viral polymerases are much more sensitive to the drug than the corresponding host enzyme
What is thymidine kinase encoded by some viruses used for? How is it pharmacologically relevant?
used in the synthesis of their DNA
it can activate some drugs in the class that target duplication of the viral genome (why? b/c it lacks specificity)
What classes of drugs does interferon fall in?
mRNA and transcription processing
AND protein translation
(note - it acts nonspecifically)
