Prevention and control of virus diseases I Flashcards
What events drastically improved life expectancy (3)?
- modern smallpox vaccine
- john snow
- the jungle - message to control the quality of food and water
What is Norovirus: how is it spread and whats the best control?
spread = oral-fecal
control = handwashing
What does hantavirus contaminate and what is the best control?
contaminate = mouse droppings
control = watch what you sweep
How can insect vectored viruses be controlled?
- insectisides
- mosquito nets
- guppys that eat mosquito larvae
- CRISPR/Cas9 gene drive –> sterilize and eradicate mosquitoes
What viruses spread like wildfire through blood exchange and what is the control?
viruses = HIV, HBV, HCV
control = safe injection sites, education, needle exchange strategies, testing blood before donation
What is the purpose of quarantine? Is it effective?
purpose = isolate infected person from the community
effective = yes, but generally a last resort
What was the first live vaccine?
Jenner’s - smallpox vaccine using vaccina virus
What are the polio vaccines?
Sabin - live attenuated oral polio (created via serial passage)
Salk - dead injectable vaccine
What was the effect of polio vaccination?
Drastic reduction in the number of paralytic cases
Describe the HPV vaccine
Garadasil - composed of the capsid L1 protein (recombinant from yeast –> very safe!)
Describe the ebola vaccine
- recombinant vaccine
- VSV glycoprotein gene replaced with ebola virus glycoprotein
- very effective
Describe mRNA vaccines (covid-19)
- lipid nanoparticles transoporting an mRNA encoding Spike protein
- lipid coat transfects cells and enhances a vaccine response
- use modified RNA bases to avoid inducing an innate immune response
Give an example of a vaccine that hasn’t worked
HIV:
- HIV subunit vaccine not protective
- live attenuated HIV vaccines are potentially dangerous
Describe how the HIV vaccine failed clinical trails
- high risk volunteers were vaccinated with adenoviruses encoding gag+pol+nef
- placebo and vaccine group had no difference
Describe how bad vaccines can be dangerous
RSV vaccine
- babies given the vaccine were more likely to be hospitalized and killed by RSV infections
- failure in Ab maturation - low affinity Abs can promote enhancement of disease
Why did antibacterial drugs come first?
- bacteria are easier to grow
- fewer protein targets
- toxicity results from effects on host cells
What different assays can be perfomed to test drug activity?
- plaque reduction assays
- enzyme inhibition assays
- activity in infected animals
- clinical trial
What is the selectivity index (SI)?
SI = CC50/EC50
CC50 - 50% cell killing concentration
What’s better, a high or low SI?
High –> implies the drug requires high concentrations to be toxic, but requires smaller concentrations to kill the virus
Where do new drugs come from?
- natural products
- chemical analogs of natural products
- chemical optimization of initial “hits”
- combinatorial chemistry
How can robotics be used in drug discovery?
robots can screen chemicals and products for antiviral activity, by automating drug application and assays
How can computational methods be used to design drugs?
- computers are used to dock model drugs in the 3D structures of proteins
- generates candidate molecules
Give an example of a drug that was a product of computer design
influenza HA inhibitors
Why is antiviral drug resistance a problem, how is it avoided
Problem:
- drugs select for resisitance
- polymerase fidelity
- quasi-species
Avoid = multi-drug modalities
