Antiviral [20] Flashcards
3 DNA viruses
Adenovirus
Herpesvirus
Papilomavirus
2 RNA viruses
Influenza virus
Retrovirus (AIDS)
Explain virus replication cycles
- Attachment to host cell
- Un-coating of virus
- Control of DNA/RNA/protein production
- Production of viral subunits
- Assembly of virions
- Release of virions (cell lysis)
Describe specificity of antiviral drugs
Hard to achieve distributional selectivity
Target enzymes, metabolic pathways, viral Nucleic acid synthesis
3 viral specific targets of antivirals
Viral cell binding
Interrupting uncoating
Stimulating host immune system
What is viral latency
Recurrence of infection
(Acute, persistent, reactivating, slow)
Are most AV drugs virustatic or viruscidal
Virustatic
No AV drugs can eliminate latency
Acute virus infection example
Influenza
Persistent virus infection example
Meningitis
Reactivating virus infection example
Herpes
Slow virus infection example
HIV
What increases AV resistance
Rapid replication rates
Spontaneous mutation
Mutations prevent protease and reverse transcriptase binding
Traits of herpes virus
Cold sores, varicella zoster (chicken pox), Epstein Barr (glandular fever)
Blisters
Infects sensory ganglia where becomes latent
Herpes treatment
Aciclovir
Synthetic guanosine analogue
High specificity to simplex
Require intracellular phosphorylation to become active
Aciclovir activation
Uses simplex’s thymidine kinase to monophosphorylate Aciclovir
Host cell kinases di and tri phosphorylate
Triphosphate form is active
Aciclovir MOA
G analogue so binds DNA
Makes a kink
DNA polymerase can’t cause elongation
HIV and AIDS general information
1981 discovery
Sexually transmitted
Destruction of host immune system
HIV1 - AIDS
HIV2 - less virulent
HIV MOA
Viral DNA -(RNA polymerase)-> viral RNA —> translation to viral components —> viral assembly —> host cell death
What does HIV target
CD4 and CD8 cells
HIV treatments
Fusion inhibitors
CCR5 inhibitors
NRTIs and NNRTIs
Protease inhibitors
Example of fusion inhibitors
Enfurvitide
Fusion inhibitor MOA
Identical to HIV gp41
Stops gp41 changing shape to allow HIV to enter host cell
Inhibits fusion of cellular and viral membranes
CCR5 inhibitor example
Maraviroc
CCR5 inhibitor MOA
Binds CCR5 receptor on CD4
Prevents interaction of gp120 and CCR5
Needed for entry to cell
Not a first line therapy
Example of nucleoside reverse transcriptase inhibitors NRTIs
Zidovudine
NRTI MOA
Inhibits viral reverse transcriptase
Active when in triphosphate form
Triphosphate competes for proviral synthesis
Termination of viral DNA elongation
Indications of NRTIs
Advanced HIV infection
Adverse effects of NRTIs
Headaches
Nausea
Anaemia
What is zidovudine structurally similar to
Thymidine
Non nucleoside reverse transcriptase inhibitors NNRTIs MOA
Doesn’t look like nucleotide
Denatures reverse transcriptase
NNRTI example
Nevirapine
Protease inhibitor example
Ritonovir
Protease inhibitor MOA
Inhibition of virus protease
Protease essential for post-translational processing of gag and gag-pol poly proteins into functional proteins
Protease inhibitors clinical pharmacology
Highly effective in suppressing viral load
CYP450 interactions
Resistance issues
Highly active anti-retroviral therapy (HAART)
NRTI + NNRTI or PI
What is atripla
One combination pill per day
What is given to HIV patients with resistant strains of HIV
Integrase inhibitors (Raltegravir)
Inhibits integration or transcribed viral DNA into host cell chromosomes
