Anti-Virals Flashcards
Structure of viruses?
- Envelope proteins
- Lipid envelope
- Genetic material (RNA or DNA)
- Capsid
What is the viral tropism of hepatitis & when is treatment required?
Tropism:
• liver hepatocyte
Only CHRONIC infection requires treatment
Hep B treatment?
Tenofovir:
• nucleoTIDE analogue
• reverse transcriptase inhibitor
• given w. Peginterferon alfa soemtimes
Hep C treatment?
Ribavirin:
• nucleoSIDE analogue
• Purine analogue
• given with Peginterferon alfa
Boceprevir:
• protease inhibitor
• most effective against HepC genotype 1
What is the goal of HCV treatment as of today and how is it achieved?
To CURE the virus
This is done with a combination of drugs which depend upon:
– HCV genotype, viral load, past treatment experience, liver health, etc
Explain DAAs (directly acting antivirals)
These are structural & non-structural proteins which we can directly target with drugs in production now
Explain the HIV life cycle
- Attachment and entry
• viral membrane proteins interact with and bind leucocyte membrane proteins –> viral capsid endocytosis - Replication and Integration
• reverse transcriptase converts viral RNA –> DNA
• DNA integrated into host DNA - Assembly and release
• host cell used to produce viral RNA & essential proteins
• virus reassembled within cell –> MATURE VIRION released
Possible areas that HIV Inhibitors can work?
(1) Attachment and Entry
• HIV Entry Inhibitors
(2a) Replication
(2b) Integration
• HIV Replication Inhibitors
(3) Assembly & Release
• HIV Replication Inhibitors
Explain how HIV Entry Inhibitors work in (1) Attachment & Entry
Normal entry of HIV:
• HIV GP120 binds CD4
• HIV GP120 also binds to either CCR5 or CXCR4
• GP41 penetrates host cell membrane and viral capsid enters
Drugs used as HIV Entry Inhibitors
o Enfuvirtide
– binds and inhibits GP41 (transmembrane glycoprotein)
o Maraviroc
– blocks CCR5 chemokine receptor.
Explain how HIV Replication Inhibitors work in (2a) Replication
Normal replication of HIV:
• Reverse transcriptase
• viral ssRNA –> dsDNA
Drugs used as HIV Replication Inhibitors in response to Replication
o NucleoSIDE RT Inhibitors
• activated by a 3-step phosphorylation process
• E.g. Zidovudine
o NucleoTIDE RT Inhibitors
• fewer phosphorylation steps required
• e.g. Tenofovir
o Non-nucleoSIDE RT Inhibitors
• NO phosphorylation required
• NOT incorporated into viral DNA
• e.g. Efavirenz
Explain how HIV Replication Inhibitors work in (2b) Integration
Normal integration of HIV:
• Viral integrase
• inserts viral RNA into host DNA
Drugs used as HIV Replication Inhibitors in response to Integration?
o Raltegravir
• viral integrase inhibitor
Explain how HIV Replication Inhibitors work in (3) Assembly & Release
Normal assembly & release:
• Gag precursor is the precursor for ALL viral structural proteins
• HIV protease cleaves the Gag precursor into an ACTIVE Gag protein
Drugs used as HIV Replication Inhibitors in response to Assembly & Release?
o Saquinavir
• Protease Inhibitor (PI)
o Ritonavir (low-dose) • reduces PI metabolism • co-administered as a booster to raise [PI]
Virology and Tropism of HSV?
Herpes Simplex Virus
Virology:
• dsDNA virus
• surrounded by a tegumet & enclosed in a lipid bilayer
Tropism:
• HSV-1 –> cold sores
• HSV-2 –> genital herpes
Treatment for HSV?
Acyclovir!
• nucleoSIDE analogue
Virology and Tropism for Influenza?
Virology:
• ssRNA virus
• Envelope proteins NEURAMINIDASE (NA) activation leads to release of virus
Tropism:
• Nose, throat and bronchi
Treatment for Influenza?
Oseltamivir
• NA inhibitor
Distinguish between different types of virus and describe how they use the host cell to replicate
HIV
• retrovirus
• leukocytes
Hepatitis
• DNA & RNA viruses
• hepatocytes
HSV
• DNA virus
Influenza
• RNA virus
