Antiviral MedChem Flashcards
1
Q
Fuzeon
A
- Long peptide (36 aa)
- Block entry to CD4+ cell
- Binds to VIRAL GP41 to inhibit cellular interaction with HIV-1 only
- Not orally active, subQ injections BID
- Also not used
2
Q
Maraviroc
A
- Selzentry
- Smaller molecule than Fuzeon
- Orally bioavailable (QD), t1/2 = 14-18 hours
- Binds host CCR5 coreceptor needed for entry by only SOME strains for HIV-1
- Needs testing for viral tropism
- Dose depends on CYP3A effects of other HIV drugs
3
Q
Maraviroc Dosing
A
- With potent CYP3A inhibitors: 150mg BID
- With NO inhibitors/inducers: 300mg BID
- With potent CYP3A inducers: 600 mg BID
4
Q
Reverse Transcriptase
A
-Inhibition widely used in HIV chemotherapy
2 Kinds:
- Nucleoside reverse transcriptase inhibitors, modified at deoxyglucose fxn. Incorporated into viral DNA by viral enzyme RT
- Non nucleoside RT inhibitors, different mechanism and site from NRTIs
5
Q
Viral Protease Inhibitors
A
- Viral proteins made in one long chain
- Protease cleaves the long chain for new viral packaging
- No protease, no new virus
- All contain amide or amide like groups
- Modified sugars that lack a 3’ -OH
6
Q
HIV Integrase Inhibitors
A
- HIV inserts copies of genome into host cells genome (hides)
- “Latent” HIV can come back out and become active again
- Integrase inhibitors prevent viral genome insertion into human CD4 cells genomes
7
Q
NS5A
A
- Dimeric protein
- Essential but mechanism isn’t understood
- 2 zinc binding portions means symmetrical or near symmetrical drugs
- Mirror image stereochems and each end is symmetric from NS5A inhibitors
8
Q
NS5B
A
- RNA polymerase that replicates viral genome
- Essential for replication
- Non-nucleoside and nucleoside versions of its inhibitors
9
Q
Sofosbuvir
A
- Sovaldi
- DFMU monophosphate has excellent activity but not well absorbed
- Oral active prodrug for DFMU-monophosphate
10
Q
Viral v.s. Bacterial Resistance
A
- Bacterial infections clear quicker while things like HIV/HCV have long term therapy
- MUCH more viral loads vs bacterial (more mutation chance)
- Viral genome replication is error prone which allows for more mutations
