Metzner

Question 1

What are the three subclass of drugs and their targets ?

Answer 1

Targeting viral proteins
Representing a false substrate
Targeting host factors.

Question 2

Give an example of a drug targeting a HIVI protein.

Answer 2

NNRTI binds at the active site of the RT, preventing movement and inhibiting the enzyme.

Question 3

Give an example of a drug targeting a host factor in HIV treatments.

Answer 3

CCR5 antagonists, change CCR5 shape and make it unusuable for virus entry.

Question 4

What are conditions for an ideal drug ?

Answer 4

Eradicate the virus without side effects
Oral availability
Easy to follow
Cheap
No resistance development

Question 5

What are the mechanisms of resistance we can differenciate ?

Answer 5

Drug resistance mutation or compensatory mutation (for fitness loss by drug treatment).

Question 6

Talking about this NNRTI nucleotide analog, what are the resistance pattern seen there =

Answer 6

There are 5 different ones. A mutation at position 188 evenn confers res. to several drugs aka cross resistance.

Question 7

What’s the two mechanisms of NRTI (nucleoside reverse transcriptase
inhibitor) resistance for HIV ?

Answer 7

Mutation of the RT so the analog cannot bind anymore

Or capacity of the RT to use ATP to excise blocking nucleosides analogs!

Question 8

How can HIV resist to the CCR5 inhibitors ?

Answer 8

Either it can modify its gp120 binding site OR it can just switch to another co receptor altogether! Like CXCR4.

Question 9

How is resistance determined and what are the difficult bits in doing so ?

Answer 9

Genetic sequencing and comparison to “wt” strain. It’s not as easy as it seems tho:because it’s difficult to know which mutation is causing which resistance.

Or phenotyping assay by doing drug concentration screening.

Question 10

What factors influence heavily the apparition of drug resistance ?

Answer 10

Drug concentration usage is really important - if it’s sub optimal, the drug doesn’t get rid of the virus but the virus develops in its presence, hence generating resistance.

Question 11

What explains HIV’s high intrapatient diversity?

Answer 11

Relatively high mutation rate that leads to each mutation occurs at least once per day: requirement to use combinations of drugs.

Question 12

What is potentcy of a drug ?

Answer 12

Ability to block virus replication. Determined by fold change in viral loads.

Question 13

What’s the genetic barrier to resistance ?

Answer 13

How many mutations the virus must accumulate to become resistant.

Question 14

What are the three factors on which development of resistant viruses (in general) is mainly due to ?

Answer 14

• Potency of drug
• Genetic barriers
• Mutation rate of the virus,

Question 15

Some parts of viruses are used in cloning vectors. Which ?

Answer 15

Enhancer sequences
Promoters
IRES
PolyA sites

Question 16

What are the two main life cycles of Bacteriophages ?

Answer 16

• Lytic phages

- Lysogenic phages (prophage integration)

Question 17

What are main factors for bacteriotherapy efficiency ?

Answer 17

• Resistance to phages
• Timing of treatment
• Stable conditions
• Neutralisation by host Abs.
• Accessibility of targets

Question 18

For what kind of diseases are gene therapies useful for ?

Answer 18

Monogenic diseases

Cancers (specific marker genes)

Question 19

What are challenges in gene therapy

Answer 19

Expression level
Duration of effect
Immune evasion of the vector
Safety
Delivery of the "drug"

Question 20

CRISPR: meaning ?

Answer 20

Clustered Regularly Interespaced Short Palindromic Repeats

Question 21

What are CRISPR spacer ?

Answer 21

A region of CRISPR regions that contain sequences from other organisms.

Question 22

How can you modify the whole population of moskitos to put a malaria resistance gene ?

Answer 22

• integrate one allel of the resistance gene using CRISPR
• DNA breaks during replication will complement with the second allele.
• Spreads within population with reproduction of moskitos