Anti-viral agents

Question 1

Acyclovir has a high specificity because?

Answer 1

The active form is only generated inside an herpes virus infected cell.

Question 2

Acyclovir and ribavirin are both antiviral agents that act as nucleoside analogues. Why is acyclovir effective against herpes simplex virus but not influenza?

Answer 2

Because acyclovir is only converted to its active form inside a cell infected by herpes virus that encodes thymidine kinase, and influenza virus does not encode such an enzyme.

Question 3

Tamiflu (oseltamivir) is an antiviral drug that can be used to treat influenza virus infection. The mechanism of action is?

Answer 3

To inhibit the neuraminidase enzyme that removes sialic acid from the infected cells surface and allow onwards spread of new virus particles.

Question 4

Two people in the world are believed to have been ‘cured’ of HIV. How has this been achieved?

Answer 4

They have undergone bone marrow transplantation with cells from a CCR5 delta 32 donor.

Question 5

4 consequences of viral genome type?

Answer 5

RNA and retro viruses have high mutation rates

RNA is unstable so RNA viral genomes are limited in size

DNA viruses have large genomes, so they have accessory genes which are lost in cultured cells

Segmented genomes allow reassortment recombination to allow rapid evolution

Question 6

6 stages of HIV replication?

Answer 6

1. GP120 protein on virus binds to CD4 receptor and possibly CCR5 or CXCR4 co-receptors
2. Viral and host membranes fuse, viral contents released into cell
3. Reverse transcriptase forms viral DNA from RNA
4. Viral DNA transported across nucleus and integrates into host DNA
5. Viral proteins produced from combined host and viral RNA
6. New viral RNA and proteins move to cell membrane and exocytosis occurs

Question 7

Cytopathic effect?

Answer 7

Virus lyses cell and debris is formed

Viruses form plaques in monolayers

Question 8

Syncytia?

Answer 8

Viruses with surface proteins can fuse at neutral pH, e.g HIV

Question 9

Detection tests for:

Viral genome?

Viral antigen?

Virus particles?

Answer 9

PCR, RT-PCR

IFA, ELISA

Electron microscopy, haemagluttination assay

Question 10

3 targets for antiviral drugs?

Answer 10

Viral enzymes

Nucleic acid replication- nucleoside analogues

Drugs that target specific viral facots are Directly Acting Antivirals

Question 11

Acyclovir?

Answer 11

Nucleoside that acts as a chain terminator

Only activated by phosphorylation of ACV to ACVMP by thymidine kinase in herpes cells

Question 12

Remdesivir?

Answer 12

Nucleoside analogue of adenosine, causes chain termination

Initially used for Hep C, tested against Ebola but didn’t meet endpoint

Question 13

Amantadine/Rimantadine?

Answer 13

Active against influenza A. Targets M2 ion channel of virus so virus cannot replicate or exocytose. Resistance can occur due to single point mutations, widely used in poultry farming

Question 14

Relenza/tamiflu?

Answer 14

Neuraminidase inhibitors- replace sialic acid as substrates for NA

Question 15

Baloxavir?

Answer 15

Inhibits viral polymerase, resistance conferred by a single point mutation

Question 16

5 targets for anti-HIV drugs?

Answer 16

1. Fusion inhibitors
2. Co-receptor antagonists
3. Protease inhibitors
4. Reverse transcription inhibitors- NRTIs, NNRTIs
5. Genome integration inhibitors- InSTIs, ALLINIs