L1 - Antiviral chemotherapy

Question 1

What does a virus need from the host cell?

Answer 1

Raw materials for synthesis

cell machinery

transport

to live

enveloped viruses - need membranes

Question 2

What are the ideal characteristics of antiviral drugs?

Answer 2

cell permeable

target critical stage of virus life cycle

no resistance

inhibition of virus protein

not active against cellular targets

Question 3

How many different genotypes of HCV?

Answer 3

7 genotypes

Question 4

how many individuals infected with HCV develop chronic liver disease?

Answer 4

85%

Question 5

Is there a vaccine for HCV?

Answer 5

NO

but there are DAAs

Question 6

What is the genome of HCV?

Answer 6

9.5Kb +sense RNA

Question 7

How many open reading frames for HCV?

Answer 7

SINGLE ORF

Question 8

What are components of the HCV genome?

Answer 8

single ORF
IRES
helices - unwinding
structural + non-structural sections

Question 9

How is HCV studied?

Answer 9

subgeneric replicon - ONLY CONTAINS REPLICATION PROTEINS

not infectious - can work in BSL2 lab

Question 10

What is a complete virus?

Answer 10

produces infectious particles

BLS3 lab

Question 11

What are the important proteins in the subgeneric replicon of HCV?

Answer 11

NS3/NS4A
NS5A
NS5B

Question 12

What is the 3rd generation inhibitor of NS3 (HCV)?

Answer 12

Voxilaprevir

Question 13

What was the issue with the 2nd generation inhibitor of NS3 (HCV)?

Answer 13

Simeprevir doesn’t work against GT3

Question 14

What was the issue with the 1st generation inhibitor of NS3 (HCV)?

Answer 14

Telaprevir, boceprevir

low barrier to resistance, side effects of skin reactions/anaemia

specific to genotype 1

Question 15

What is the inhibitor of NS5B that is a nucleoside analogue?

Answer 15

SOFOSBUVIR

Question 16

What is the inhibitor of NS5B that is a non-nucleoside analogue?

Answer 16

DASABUVIR

Question 17

What are the inhibitors of NS5A?

Answer 17

target Domain I

DACLATASVIR (low resistance)

VELPATASVIR (pan-genotypic)

Question 18

What is the function of NS3 in HCV?

Answer 18

protease/helicase

Question 19

What is the function of NS5B in HCV?

Answer 19

RNA polymerase

Question 20

What is the function of NS5A in HCV?

Answer 20

virus RNA replication
virus assembly
binds viral RNA
binds cellular factors

Question 21

What is the recommended therapy for HCV?

Answer 21

12 week therapy

Question 22

How many proteins does EBOV make?

Answer 22

7 proteins

Question 23

What are the 4 proteins needed for EBOV replication?

Answer 23

NP
VP35
VP30
L

Question 24

What is the EBOV mini-genome replication assay?

Answer 24

make cDNA copies of the 4 proteins

clone into plasmids

transfect into cell lines

mini-genome with luciferase

quantitative measure of light

Question 25

What is the in silicons drug design involving the NP/VP35 interaction of EBOV?

Answer 25

identify compounds that compete with VP35 to bind to NP - blocking EBOV genome replication

3 hotspots to target

Question 26

What is the candidate EBOV antiviral drug?

Answer 26

MCCB4 - binds to hotspots 1 & 2

Question 27

What is the EC50 for EBOV mini genome?

Answer 27

4.8uM

Question 28

How can we prove that MCCB4 targets NP (EBOV)?

Answer 28

mutagenesis

mutations to alanine show an increase in EC50 and resistance