Prevention and control of virus diseases I

Question 1

What events drastically improved life expectancy (3)?

Answer 1

1. modern smallpox vaccine
2. john snow
3. the jungle - message to control the quality of food and water

Question 2

What is Norovirus: how is it spread and whats the best control?

Answer 2

spread = oral-fecal
control = handwashing

Question 3

What does hantavirus contaminate and what is the best control?

Answer 3

contaminate = mouse droppings
control = watch what you sweep

Question 4

How can insect vectored viruses be controlled?

Answer 4

1. insectisides
2. mosquito nets
3. guppys that eat mosquito larvae
4. CRISPR/Cas9 gene drive –> sterilize and eradicate mosquitoes

Question 5

What viruses spread like wildfire through blood exchange and what is the control?

Answer 5

viruses = HIV, HBV, HCV
control = safe injection sites, education, needle exchange strategies, testing blood before donation

Question 6

What is the purpose of quarantine? Is it effective?

Answer 6

purpose = isolate infected person from the community

effective = yes, but generally a last resort

Question 7

What was the first live vaccine?

Answer 7

Jenner’s - smallpox vaccine using vaccina virus

Question 8

What are the polio vaccines?

Answer 8

Sabin - live attenuated oral polio (created via serial passage)

Salk - dead injectable vaccine

Question 9

What was the effect of polio vaccination?

Answer 9

Drastic reduction in the number of paralytic cases

Question 10

Describe the HPV vaccine

Answer 10

Garadasil - composed of the capsid L1 protein (recombinant from yeast –> very safe!)

Question 11

Describe the ebola vaccine

Answer 11

• recombinant vaccine
• VSV glycoprotein gene replaced with ebola virus glycoprotein
• very effective

Question 12

Describe mRNA vaccines (covid-19)

Answer 12

• 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

Question 13

Give an example of a vaccine that hasn’t worked

Answer 13

HIV:
- HIV subunit vaccine not protective
- live attenuated HIV vaccines are potentially dangerous

Question 14

Describe how the HIV vaccine failed clinical trails

Answer 14

• high risk volunteers were vaccinated with adenoviruses encoding gag+pol+nef
• placebo and vaccine group had no difference

Question 15

Describe how bad vaccines can be dangerous

Answer 15

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

Question 16

Why did antibacterial drugs come first?

Answer 16

• bacteria are easier to grow
• fewer protein targets
• toxicity results from effects on host cells

Question 17

What different assays can be perfomed to test drug activity?

Answer 17

1. plaque reduction assays
2. enzyme inhibition assays
3. activity in infected animals
4. clinical trial

Question 18

What is the selectivity index (SI)?

Answer 18

SI = CC50/EC50

CC50 - 50% cell killing concentration

Question 19

What’s better, a high or low SI?

Answer 19

High –> implies the drug requires high concentrations to be toxic, but requires smaller concentrations to kill the virus

Question 20

Where do new drugs come from?

Answer 20

• natural products
• chemical analogs of natural products
• chemical optimization of initial “hits”
• combinatorial chemistry

Question 21

How can robotics be used in drug discovery?

Answer 21

robots can screen chemicals and products for antiviral activity, by automating drug application and assays

Question 22

How can computational methods be used to design drugs?

Answer 22

• computers are used to dock model drugs in the 3D structures of proteins
• generates candidate molecules

Question 23

Give an example of a drug that was a product of computer design

Answer 23

influenza HA inhibitors

Question 24

Why is antiviral drug resistance a problem, how is it avoided

Answer 24

Problem:
- drugs select for resisitance
- polymerase fidelity
- quasi-species

Avoid = multi-drug modalities

Question 25

What are some selection pressures for viruses?

Answer 25

• immune defenses
• competition with other viruses
• host-to-host transmission efficiency
• drugs