Antiviral use Flashcards
List some infections treated with antiviral agents.
DNA viruses: Herpes simplex 1 and 2 Varicella-zoster Cytomegalovirus Epstein Barr virus Human herpes-virus 8 Hepatitis B
RNA viruses:
Influenza
Human Immunodeficiency virus
Hepatitis C
Describe what needs to be considered when designing an anti-viral drug.
Burden of disease and clinical need Understanding virology: what to target Drug development: - Screening compounds or drug design Clinical trials and impact Adverse effects Resistance and monitoring
Name the three types of influenza virus
Influenza A - Multiple host species - Antigenic drift and shift Influenza B - No animal reservoir - Lower mortality Influenza C - Common cold like
Describe how an influenza virus enters and replicates in a cell.
It enters the cell by endocytosis, forming an endosomal vesicle
Then it is uncoated from the endosomal vesicle through the use of M2 ion channels that let H+ into the cell
Then it uses ran replication to synthesise new viruses
And they then bud with the cell membrane and exit the cell
This requires an enzyme - neuraminidase - to release the virus from the surface of the cell
What are the mechanisms by which you can treat an influenza viral infection?
By stopping the virus from attaching to the cell membrane and then entering via endocytosis, vaccine does this
By blocking the M2 ion channel, so the virus can’t uncoat
By stopping the virus from unbinding with the cell membrane so it can’t spread, neuraminidase inhibitor
Tell me about amantadanes
M2 ion channel inhibitors
Amantadine and Rimantadine
Anti-parkinsonism activity
Tricyclic amines block M2 channel to inhibit viral uncoating
Active against influenza A including non-human subtypes
What are the clinical limitations of amantadanes?
Spectrum: Influenza A only
Side effects: Central nervous system
Renal excretion (amantadine)
Single point mutation in M2 gene: S31N
- High-level, rapid emergence resistance
- Transmissable
Explain the action of neuraminidase and why it is a good potential target for antivirals.
Neuraminidase is an enzyme on influenza viruses surface that is responsible for unbinding viruses from the surface of cells they have infected.
It is a good potential target for antivirals because:
- Active site is conserved across subtypes:
- Human an non-human influenza A
- Influenza B
- M2 resistant viruses
- Avian strains including H5N1
- Reconstructed 1918 pandemic H1N1
How does a neuraminidase inhibitor work?
It inhibits neuraminidase
It can block the active site of the neuraminidase enzyme on influenza viruses (Oseltamivir)
There by stopping them from unbinding from cells
They then aggregate on the surface of the infected cell
The immune system can easily get rid of them
Name some neuraminidase inhibitors.
Zanamivir - Low bioavailability - Dry powder aerosol - Remains undetectable in sputum up to 24 hours post dosing - Renally excreted
Oseltamivir
- Prodrug
- 80% bioavailability
Give some of the effects that were shown by use of Oseltamivir in phase III trials.
Reduced the illness duration of influenza infected patients
Reduced the severity of illness in influenza infected patients
The earlier the treatment the bigger the improvement in illness duration in influenza infected patients
Reduced mortality rates in influenza infected patients
How effective is Oseltamivir as seasonal prophylaxis?
It reduced the onset of influenza infection by 76%
What are some of the adverse events of Oseltamivir?
Vomiting
Abdominal pain
Epistaxis
Tell me about Oseltamivir resistance.
There is a resistance to Oseltamivir in H5N1 (bird flu)
How is resistance surveillance carried out?
Influenza WHO system
Neuraminidase Inhibitor Susceptibility Network (NISN)
National and European surveillance
Detailed evaluation of post treatment isolates
