Mechanism Of Action Of Antivirals Flashcards
Why do we need anti viral drugs?
There are poorly effective vaccines for some viruses important to human health
Not everyone can be administered a vaccine
Immune response to vaccine can take time
What are some examples of current uses of anti-viral drugs?
Treatment of acute infection
Treatment of chronic infection
Post exposure prophylaxis and preventing infection - HIV
Pre exposure prophylaxis- HIV
Prophylaxis of reactivated infection
How do we inhibit viral replication without harming the infected cell?
Target protein in virus, not infected cell
Due to the differences in structure and metabolic pathways between host and pathogen
What occurs in a virus life cycle?
1.:Recognition
- Attatchement
- Penetration
- Uncoating
- Transcription
- Protein synthesis
- Replication
- Assembly / envelopment
- Lysis and release / budding and release
What are the modes of action of selected antivirals?
Preventing viral absorption into host cell
Preventing penetration
Preventing viral nucleic acid replication
Preventing maturation of virus
Preventing virus release
What are the advantages of using viral encoded enzymes as targets for antivirals?
As they have minimal effect on host enzymes or processes
Why is it so difficult to develop effective anti viral drugs?
Viruses use cellular proteins which may have other functions
Viruses must replicate inside cells
Viruses take over the host cells replicative machinery
Viruses have a high mutations rate
Some viruses are bake to maintain they’re latent state
Some viruses are able to integrate they’re genetic material into host cells
What are the four types of herpes viruses?
Herpes simplex (HSV)
Varcella Zoster virus (VZV)
Cytomegalovirus (CMV)
Epstein Barr virus (EBV)
Why is Aciclovir a effective and selective antiviral?
Is activated to active drug by viral enzyme TK by increasing the number of phosphates on the ACV
The viral polymerase only integrates the active form of ACV
What is Glanciclovir?
Active for CMV - reactivated infection in organ transplant patients
Structurally similar to aiclovir
CMV Does not encode TK but has UL97 kinase
Inhibits CMV DNA polymerase
What is foscarnet?
Selectively inhibits viral DNA/RNA polymerases and RTs
No reactivation required
Binds pyrophosphate binding site - a structural. Mimic
Used for CMV
May be used for ganciclovir resistance
What is cidofovir?
Chain terminator antiviral - targets DNA polymerase
Monophosphate nucleotide analog
Prodrug - phosphorylated by cellular kinases to di-phosphate
Drug active against CMV - BUT MUCH MORE NEPHROTOXIC
Treatment of retinitis in HIV disease
What are the two main mechanisms of resistance to anti-virals in herpes viruses?
Thymidine kinase mutants
DNA polymerase mutants
If occurs in TK- drugs NOT needing activation are still effective
If occurs in DNA polymerase- all drugs rendered less effective
VERY RARE IN IMMUNE COMPETENT PATIENTS
What are the four types of anti-HIV drugs?
Anti reverse transcriptase drugs
Protease inhibitors
Integrase inhibitors - POL Gene
Fusion inhibitors
How is HIV treated?
Highly active anti retroviral therapy - HAART
Combination of drugs to avoid resistance
How is reverse transcriptase (RT) inhibited by nucleoside inhibitors?
EG. ZIDOVUDINE
Synthetic analogue of nucleotide thymidine
When converted to tri-nucleotide by cell enzymes RT is blocked by
- competing for nucleotide substrate dTTP
- incorporation into DNA causing chain termination
How is reverse transcriptase (RT) inhibited by non-nucleoside inhibitors?
EG. NEVIRAPINE
Non competitive inhibitor of HIV-1 RT
Synergistic with NRTIs such as AZT because of different mechanis
What are the problems with treating HIV?
Mutation rate - high
Viral load - high
Resistance
Forms quasispecies from switching a individual patient - a viral swar
Hence using HAART
How does Amantadine act as a antiviral for influenza?
Inhibit viral Uncoating by blocking M2 protein when inside cells
Now rarely used
How does Zanamivir and osektamivir act as a antiviral for influenza?
Inhibits virus release from infected cells via inhibition of neuraminidase
Describe how Zanamivir and osektamivir act as a antiviral for influenza
Target and inhibit NA (neuraminidase) at highly conserved site
Prevent release of siapic acid residues from the cell receptor
Preventing virus budding and release and spread to adjacent cells
How can influenza become resistant to anti virals?
Point mutation
Likely to be selected from among quasispecies during treatment
Transmissible and virulent
Remains sensitive to zanamivir
What is hepatitis C virus?
Transmitted vis blood - mother to baby
Increasingly common
Major cause of chronic liver disease
Vaccination NOT available
Early treatment facilitates resolution
How does Ribavirin act as a antiviral for RSV and HepC?
Block RNA synthesis by inhibiting inosine 5-monophosphate (IMP)
This blocks the conversion of IMP to XMP
Thereby stopping GTP synthesis and RNA synthesis
Why are direct acting anti virals (DAA) used to treat hepatitis C?
Relatively new class of medication
Acts to target specific steps in the HCV viral life cycle
Shorten the length of therapy, minimise side effects, target the virus itself
Structural and non-structural proteins - replicate and assemble new virons
How does DAA function?
By inhibiting ajar HCV induced enzymes that are essential for HCV replication and are potential drug targets
Have different viral targets and are synergistic in combinations
What is occupational infection?
Infection in a health care setting
- sharps
- splashes
- blood born viruses
What is post exposure prophylaxis
Emergency rapid treatment for infection
What are some examples of incurable viral infections?
Rabies
Dengue
Ebola
HPV
Common cold viruses
