Medchem of Antivirals Flashcards
Fuzeon treats which virus?
HIV
Fuzeon moa
blocks entry to CD4+ cell and binds to viral GP41 to inhibit cellular interaction with HIV1
Fuzeon dose
subQ 2x daily
Why is Fuzeon not used?
Poor compliance and cost
Maraviroc
Selzentry
Maraviroc moa
binds CCR5 coreceptor needed for entry by only some strains of HIV-1
Maraviroc dosing with potent CYP3A inhibitors
150 mg daily
Maraviroc dosing with no potent CYP3A inhibitors or CYP3A inducers
300 mg twice daily
Maraviroc dosing with potent CYP3A inducers
600 mg twice daily
What are 2 different kinds of inhibitors of reverse transcriptase to treat HIV
nucleoside reverse transcriptase
non-nucleoside reverse transcriptase inhibitors
What is structurally different for nucleoside reverse transcriptase inhibitors?
Modified deoxyglucose function, with no 3’ OH group
Phosphorylated by cell kinases that are incorporated in viral DNA by the viral enzyme RT
Viral proteins made as one long read through protein then cleaved by protease
Viral protease inhibitors
Protease inhibitor drugs end in
-vir
NRTIs end in
-dine
-bine
pluse didanosine and abicavir
HIV inserts copies of its genome as DNA into host cells genome where it hides out
This “latent” HIV can come back out and become active virus again
integrase inhibitors
Prevent viral genome insertion into human CD4 cell
integrase inhibitors
integrase inhibitors end in
-gravir
2 zinc binding portions mean symmetrical or near symmetrical drugs
NS5A inhibitors in HCV
NS5A inhibitors end in
-svir
RNA polymerase that replicated viral genome (RNA virus)
NS5B
RNA dependent RNA polymerase
NS5B
NS5B drugs end in
-buvir
Sofosbuvir
Sovaldi
Sofosbuvir is the active prodrug of
DFMU monophosphate
NS3/NS4B protease and HCV protease inhibitors.
ends in
-previr
Why do we not see so much resistance development in bacterial therapy (with rare exceptions) yet we have to cover several sites? `
- time - HIV/HCV longer term therapy
- Viral loads are higher so more chance of mutant
- Viral genome replication more error prone
drug combos with >1 MOA are usually
more effective and produce less resistance during therapy
