Antiviral vaccines & chemotherapy Flashcards
What is the difference between passive and active immunisation?
Passive: Given Aby = neutralise Ag (e.g. toxin). I.Sys not involved = short term protection
Active: Given Ag = I.sys involved = make Aby. Long term protection (-prophylaxis)
How are viruses attenuated?
- removal of virulent genes
- modify growth cond.: temp, lo [O2], substances in growth media
a) why are adjuvants used?
b) Describe the actions of adjuvants
a) enhance immunogenicity to vaccine
b) stimulate innate immune resp -> initiate adaptive immune resp
What are the advantages of the mRNA and Adenovirus vaccines.
- stimulate immune response
- no Adjuvant needed
- NA not integrated in host genome
What are “Prodrugs” and what advantages do they have?
- have chemical side group on antiviral molecule > activates the antiviral when profrug is cleaved by host enz
= enhance adsorption & tiss penetration to oral drugs
Aciclovir is active in cells infected by Herpes viruses and not in uninfected cells. Why?
*note infected cells must be dividing
Herpes-infected cells have herpes thymidine kinase that phosphorolates drug -> monophosphate -> triphosphate = active agent -> binds & inhibits herpes V DNA pol.
* also once drug is phosphorylated can’t escape cell
Uninfected cells don’t have enz.
What are the current anti HCV drugs directed against, how do they work?
- Daclatasvir, ledipasvir, omitasvir: NS5a = *RNA dependent RNA pol
- Sofosbuvir: NS5b *RNA dependent RNA pol
- Paritaprevir, Ritonavir?: NS3/4a = protease inhibitor
Describe the action of Amantadine in influenza infections.
- Bind to M2 protein = block ion channel = H+ not enter virus = no dec in pH = no uncoating of virus = not release RNA = no replication in host cell nucleus
What is HAART?
Highly active anti-viral therapy
- combination of chemotherapy drugs (against HIV)
What anti COVID drugs are used in Australia? What are the actions of these drugs?
- Nirmatrelvir/Ritonavir: Protease inhibitors = prevent peptide cleaving
- Molnupiravir/Lageviro: Induces copy errors during RNA replication (lethal mutagenesis)
Briefly explain the role/mechanism of interferons as anti viral agents.
- When virus infects host cell, interferon genes turned on => interferon made. Cell dies
- Interferon stimulates production of antiviral protein in another cell
- Antiviral proteins block reproduction in that cell
Describe the action of AZT (Zidovudine) on HIV.
- In un&infected cells, AZT phosphorylated => active triphosphate form
- bind & inhibit RVS transcriptase ≠ RVS transcription
.2. Stop nucleotide addition = Prevents NA elongation
*Can be toxic since also effect uninfected cells
Describe the actions of Fomivirsen & site administered to in treatment of __
- ssDNA complementary to viral mRNA = prevent translation
- administered to eye = treat CMV retinititis
When is Dexamethasone administered for COVID19 & what it does
- Given LATE in disease for pts struggling to breathe
- Immunosuppressive = stops cytokine storm
*counterproductive if used early
When is Remdesivir administered for COVID19 & what it does
- Effective in Early infection (& used for Ebola V)
- Stops RNA extension/replication
What is REGEN COV2 for COVID19 & what it does
2 monoclonal Aby:
- REGN10933 (casirivimab): bind to S1 = prevent attachment
- REGN10987 (imdevimab): bind to S2 = prevent fusion (b/w viral & host memb = not enter)
The differences b/w inactivated & live attenuated vaccine in traditional vaccines
- Inactivated vaccines (killed virus)
- Have antigenicity w/out ability to infect, but require adjuvants
- Make Aby against envelope / capsid proteins - Live attenuated
- Alive but lost ability to cause disease & usually not require adjuvants
- more successful bc mimics real infection
- risk of causing infection
Describe these 3 protein vaccines
a) Subunit vaccines
b) Synthetic vaccines
c) Virus like particles (HPV)
a) isolating a protein / carbo from virus that illicit good I.Resp.
b) 1º structure of proteins & peptide chains but may not be recognised by I.Sys
c) Just use capsomere w/out DNA/RNA
*All require adjuvants
Describe these 3 Gene-based vaccines
a) Viral vectors
b) mRNA vaccines
c) Gene vaccines
a) Stimulate I.Resp w/out adjuvant & DNA not integrate in host genome e.g. adenovirus vector carrying spike protein DNA sequ.
b) mRNA vaccine in lipid nanoparticle - can stimul. I.Resp. *Heat labile
c) Inject viral genes directly onto muscle / skin = expression on cell surface
5 Ideal features for a vaccine
- Effective: provide protective immunity over durtion
- Available: produce lrg supply
- Stable (w/ temp, humidity) e.g. mRNA is heat labile
- Cost
- Safety (no adverse side effects)
a) chemotherapeutic index equation
b) range of effective drugs
a) = inhibitory dose ÷ toxic dose
b) 100-1000
6 point of actions for antivirals
- Bind to free viral particle
- Interfere w/ V adsorption (binding to rceptor)
- Inhibit V coating
- Inhibit viral transcription & replication e.g. RNA dependent RNA polymerase
- Disrupt cell. processing of viral particles (but cellular proteins might be similar to host = damage)
- Interfere w/ V maturation or budding: inhibt release of virus
