Anti-virals Flashcards
describe the structure of viruses
- genetic material = RNA/DNA
- capside around genetic material
- some viruses have lipid envelope that is decorated by envelope proteins
what do Hep B and C have a tropism for?
liver hepatocytes
is Hep B curable? what does this mean for treatment?
- not curable
- all you can do is contain viral replication
- transform it into a chronic disease that is less likely to cause cirrhosis/ liver failure/ cancer
at what point do you start Hep B/C treatment?
- a lot of people can clear Hep B/C before they get chronic infection
- infected person should be left for 6 months to see if their immune system will clear it
- if not, need treatment
what is the difference between a nucleoside and a nucleotide?
- nucleoside = base and sugar
- nucleotide = base + sugar + phosphate
what is the treatment for Hep B?
- Tenofovir = nucleotide analogue, reverse transcriptase inhibitor
- competes w/ endogenous deoxynucleotides that would be used to make up DNA
- block synthesis and generation of more DNA
what is the treatment for Hep C?
- Ribavarin and peginterferon alpha
- Boceprivir
how do ribavarin and peginterferon alpha work?
compete with endogenous nucleosides, prevents synthesis of RNA
how does Boceprivir work?
- protease inhibitor
- effective against Hep C genotype 1 (most common)
- once viral genome has been replicated, certain proteins need to be cleaved to form full virus
- if these are blocked, correct components are not produced
describe the attachment and entry into HIV life cycle
- viral membrane proteins interact w/ leukocyte membrane receptors
- leads to viral capsid endocytosis
- HIV GP120 attached to CD4 receptor on T lymphocytes
- GP120 also binds to either CCR5 or CXCR4
- GP41 then penetrates host cell membrane and viral capsid enters
describe the replication and integration in HIV life cycle
- within cytoplasm, there is reverse transcriptase
- converts RNA –> DNA
- DNA transported into nucleus, integrated into host DNA
describe assembly and release in HIV life cycle
- host cell machinery used to produce copies of viral RNA and essential proteins
- assembled to form new virus particles and mature virions are released
name 2 HIV entry inhibitors and how they work
- enfuvirtide: binds to GP41 on HIV and blocks fusion of virus with host cell membrane
- Maraviroc: blocks CCR5 receptor
what is the significance of having a polymorphism in CCR5 receptor?
HIV can infect them but it can’t enter their cells
what is reverse transcriptase?
- Viral RNA converted to double stranded DNA by reverse transcriptase
what do nucleotide/ nucleoside reverse transcriptase inhibitors do?
- Compete with endogenous deoxynucleotides/deoxynucleosides
- inhibit action of reverse transcriptase
Give an example of a nucleotide and a nucleoside reverse transcriptase inhibitor
Nucleoside = Zidovudine Nucleotide = Tenofovir
how do non-nucleotide reverse transcriptase inhibitors work?
- Not incorporated into DNA
- Bind to reverse transcriptase
- Cause change in shape of enzyme –> block HIV replication
- E.g. Efavirenz
what is the MoA of HIV integrase inhibitors?
- Viral integrase inserts viral DNA into host DNA
- Integrase inhibitor = Raltegravir
what happens once the viral RNA has been replicated?
- Capsid produced
- Virus needs to produce some other components to be synthesised to make it complete virus that can infect other cells
- Gag gene encodes ALL viral structural proteins
what does HIV protease do?
- cleaves Gag precursor proteins
- releasing proteins that go on to make up complete virus
name a HIV protease inhibitor. what is it used with?
- Saquinavir = 1st gen protease inhibitor, low bioavailability so not very good drug
- Low dose ritonavir = reduces metabolism of protease inhibitor (saquinavir) allows squinavir to reach therapeutic concentrations
describe the structure of the Herpes Simplex Virus
- dsDNA virus
- surrounded by tegument and enclosed in lipid bilayer
what is the tropisms of HSV?
- HSV1 = cold sores
- HSV2 = genital herpes
what is the treatment of HSV?
- acyclovir: nucleoside analogue
- very specific drug, one phosphorylation steps requires viral kinases
describe the structure of influenza
- Multipartitie single stranded RNA virus
- Envelope protein neuraminidase important in release of virus into host cell
what is the tropism of influenza?
- nose
- throat
- bronchi
what drug can be used in influenza treatment?
- Oseltamivir: neuraminidase inhibitor
- Approved for treatment of influenza A and B and prevention of influenza
