Anti-Virals Flashcards
what are some viral targets for drugs?
- viral capsid proteins
- viral integrase (HIV)
- proteases
name some features of viruses
- envelope proteins
- lipid envelope
- capsid (protein shell)
- genetic material (RNA or DNA)
what is the tropism in hepatitis?
liver hepatocytes
what sort of hepatitis infection requires treatment?
chronic infection only (B and C)
what drugs are used to treat hep B?
tenofovir (nucleoTide analogue)
this is for chronic management and is not a cure
what is tenofovir? (HepB)
a nucleotide analogue that inhibits reverse transcriptase
given with peginterferon alpha
what drugs are used to treat Hep C?
- Ribavirin (nucleoSide analogue)
- Boceprevir (protease inhibitor)
what is ribavirin?
nucleoside analogue
• Purine analogue.
• Given with Peginterferon alfa.
Use for Hep C
what is tenofovir used for?
hep B treatment and HIV (inhibit reverse transcriptase)
what is ribavirin used for?
hep C treatment
what is boceprevir used for?
hep C treatment
what is boceprevir?
protease inhibitor
•Most effective against HepC genotype 1.
how does the hep B and hep C virus differ?
hep B is a dsDNA virus while hep C is a ssRNA virus
which hepatitis infection can be cured?
C can be cured while B cannot be cured
hep C is given a combo of drugs based on the HCV genotype, viral load, past treatment experience and liver health etc
what are the stages of HIV’s life cycle?
1) attachment and entry
2) replication and integration (these can be targetted separately)
3) assembly and release
what happens in the attachment and entry stage of HIV?
viral membrane proteins interact and bind leucocyte membrane proteins leading to viral capsid endocytosis.
Use GP120 and GP41
what happens in the replication and integration stage of HIV?
reverse transcriptase converts viral RNA to DNA which is integrated into host DNA by HIV integrase
how does HIV enter a cell?
HIV GP120 binds CD4 and either CCR5 (chemokine receptor) or CXCR4.
what needs to be done for HIV to definitely enter a cell?
needs to bind to the chemokine co-receptor CCR5 or CXCR4 alongside the binding to CD4
what part of HIV penetrates the membrane of the host?
Gp41
glycoprotein 41: envelope protein complex subunit in retroviruses
what drugs can be used to target the attachment and entry phase of HIV’s life cycle?
- enfuvirtide (binds and inhibits Gp41)
- maraviroc (blocks CCR5 co-receptor)
what does enfuvirtide do?
binds to Gp41 of the HIV virus to disable penetration into the host cells membrane
what does maraviroc do?
blocks to CCR5 so viral endocytosis can not be stimulated
how does HIV replicate normally?
Reverse transcription
– viral ssRNA becomes dsDNA.
what drugs can be used to target HIV replication (reverse transcription) ?
o Zidovudine/AZT
– nucleoside RT inhibitor.
o Tenofovir
– nucleotide RT inhibitor.
o Efavirenz
– non-nucleoside RT inhibitor.
what is zidovudine?
nucleoside RT inhibitor
Activated by a 3-step phosphorylation process.
what is tenofovir? (HIV)
nucleotide RT inhibitor
Activated by fewer (<3) phosphorylation steps
what is efavirenz?
non-nucleoside RT inhibitor (use in HIV)
- No phosphorylation required as it is not incorporated into viral DNA.
- Binds to RT and changes its conformation
which of the drugs that target HIV replication has the least phosphorylation steps?
efavirenz (no phosphorylation required)
what mutation in some people means they do not become infected by HIV?
delta 32 mutation of CCR5
what is the effect of having a delta 32 mutation?
the cells do not express the chemokine receptor CCR5 and therefore HIV cannot be endocytosed
how does HIV integrate its genetic material into the human genome?
Viral integrase inserts viral RNA into host DNA.
what drugs target HIV integration?
Raltegravir – viral integrase inhibitor.
what does raltegravir do?
viral integrase:
inhibits HIV viral RNA being integrated into human DNA by inhibiting HIV integrase
how does HIV assemble and release its virions?
o Gag precursor is the precursor for all viral structural proteins.
o HIV protease cleaves the Gag precursor into an active Gag protein to be used for make viral components
what drugs target HIV assembly and release?
target HIV protease that cleaves Gag precursor o Saquinavir – protease inhibitor o Low-dose Ritonavir – reduces protease inhibitor metabolism.
what are the HIV protease inhibitors?
o Saquinavir
o Low-dose Ritonavir (booster given to increase concentration of protease inhibitors)
what are the HIV integrase inhibitors?
Raltegravir
what are the HIV replication inhibitors?
o Zidovudine (nucleoside RTi) o Tenofovir (nucleotide RTi) o Efavirenz (non-nucleoside RTi)
what are the HIV entry inhibitors?
o Enfuvirtide (GP41) o Maraviroc (CCR5)
what are the stages of HIV life cycle split up according to drug targeting?
- virus attachment
- virus entry
- virus replication
- virus integration
- virus assembly and release
what sort of virus is Herpes Simplex?
dsDNA
like Hep B
describe HSV structure
o Surrounded by a tegumet & enclosed in a lipid bilayer.
what are the tropisms of HSV-1 and HSV-2?
o HSV-1 –> cold sores (oral)
o HSV-2 –> genital herpes (genital)
how is HSV infection treated?
Acyclovir
– nucleoside analogue.
what is the difference between a nucleoside and nucleotide?
nucleoside= base+ sugar
nucleotide= base+ sugar+phosphate
what sort of virus is influenza?
ssRNA
like Hep C
describe the Influenza structure
Envelope proteins neuraminidase (NA) activation leads to release of virus
what is the tropism for influenza?
Nose, throat and bronchi.
what is the treatment for influenza?
Oseltamivir
– Neuraminidase inhibitor.
what is neuraminidase?
enzymes cleave the glycosidic linkages of neuraminic acids.
Found on Influenzavirus
what sorts of viruses are the following:
- HIV
- Hep B
- Hep C
- HSV
- Influenza
- HIV–> retrovirus
- Hep B–> dsDNA
- Hep C–> ssRNA
- HSV–> dsDNA
- Influenza–> ssRNA
name some nucleoside analogues and the infections they treat
ribavirin–> HepC
acyclovir–> Herpes Simplex
name a neuraminidase inhibitor and the infection it treats
oseltamivir –> influenza
