4.10 Anti-Virals

Question 1

What are viruses?

Answer 1

Obligate intracellular parasites

Question 2

Which anti-viral has the highest level of specificity?

Answer 2

Acyclovir

Question 3

What condition is acyclovir used to treat?

Answer 3

Herpes

Question 4

Why is acyclovir so specific?

Answer 4

It has to be phosphorylated from ACV to AVCMP by thymidine kinase which is only present in herpes virus infected cells

Question 5

How does acyclovir work as antiviral?

Answer 5

As a nucleoside analogue

It is a chain terminator as it lacks a 3’ OH group, thus phosphodiester bonds cannot form, preventing viral replication

Question 6

What is a nucleoside inhibitor?

Answer 6

Molecule which looks like a nucleoside and is therefore incorporated into the genome, but actually inhibits viral replication

Question 7

What is RNA in the negative sense?

Answer 7

A strand of RNA which is complementary to the mRNA

Question 8

What sense of genetic material can ribosomes translate?

Answer 8

Positive sense

Question 9

What is a virion?

Answer 9

A virus particle outside the cell

Question 10

Why can ribosomes not be targeted in anti-viral medications?

Answer 10

Viruses uses human ribosomes to replicate, meaning they would be attacked

Question 11

What is the central dogma?

Answer 11

DNA is converted by transcriptase into RNA which is translated by ribosomes into proteins

Question 12

Why do viruses have a high mutation rate?

Answer 12

They use their own polymerase to replicate which LACK PROOF READING

Question 13

RNA is shorter than DNA. How do RNA viruses compensate for this?

Answer 13

RNA viruses use complex encoding strategies to make more proteins than expected

Question 14

Why is it useful for DNA viruses to be large?

Answer 14

They have room to acquire accessory genes which could make that virus better at modifying host immune response

Question 15

What is a segmented genome and how does this impact viruses?

Answer 15

Allows easy recombination – reassortment

If different strains of same virus enter cell, the DNA can be mixed to give a mutated virus

Question 16

What is the size range of viruses?

Answer 16

1nm to 1 micrometer

Question 17

What are two examples of neuramidase inhibitors?

Answer 17

Tamiflu and relenza

Question 18

What is remdisivir a nucleoside inhibitor of?

Answer 18

Adenosine

Question 19

How does remdisivir work as a nucleoside inhibitor?

Answer 19

Acts as adenosine and causes chain termination 3 nucleosides later due to the twisting of the molecule

Question 20

What is remdisivir used to treat?

Answer 20

Hepatitis C

Question 21

What are 2 examples of adamantanes?

Answer 21

Rimantadine, amantadine

Question 22

How does amantadine work as an antiviral?

Answer 22

Blocks the M2 ion channel so that H+ cannot enter the endosome

Thus the virus is trapped inside the endosome and cannot replicate

Question 23

Why is the use of amantadine not recommended?

Answer 23

Most H3N2 viruses are resistant to it

A single point mutation can mean that amantadine cannot bind M2

Question 24

How do neuraminidase inhibitors (e.g. antiviral tamiflu) work?

Answer 24

Inhibits the action of neuraminidase, preventing viral release and infection of more host cells

Question 25

How do neuraminidases (e.g. sialidase) work normally?

Answer 25

They cleave bonds between **haemagluttinin** on influenza and **sialic acid** on host cell membrane, causing **viral release**

Question 26

What are tamiflu and relenza used to treat?

Answer 26

Influenza

Question 27

What is the lipid envelopes of viruses derived from?

Answer 27

The host cell membrane

Question 28

What is the cell membrane of a non-enveloped virus made from?

Answer 28

Protein capsid

Question 29

In **cultured** cells, why are some genes in virus’ genome lost?

Answer 29

Some genes limit the **host cell immune response** to give the virus an advantage In cultured cells, there is no immune response so these genes are not needed

Question 30

What are the stages of viral replication? **AITAE**

Answer 30

Attachment – of attachment proteins to membrane receptors Insertion – of nuclear capsid with viral genome Translation – into viral proteins Assembly – of proteins into viral material Exocytosis – of virus from host cell

Question 31

What do direct acting antivirals target?

Answer 31

Specific viral factors

Question 32

What are biologicals?

Answer 32

Antibodies which are derived from recovered individuals or synthesized in the lab from immobilized B cells Given directly into the blood

Question 33

What anti-virals are used to treat hepatitis C?

Answer 33

Direct Acting Antivirals

Question 34

Between Relenza and Tamiflu, which is more effective and why?

Answer 34

Tamiflu – the chemistry of relenza means the virus can more readily acquire resistance so less effective

Question 35

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

Answer 35

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 36

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

Answer 36

To **inhibit the neuraminidase enzyme** that removes sialic acid from the infected cells surface This prevents onwards spread of new virus particles

Question 37

Why might a patient with chronic hepatitis C virus treated with an HCV protease inhibitor drug show a loss of a positive viral response over time?

Answer 37

The virus has **acquired resistance** to the drug The patient has acquired a second infection with a **different strain** of HCV The patient has **stopped taking** the drug

Question 38

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

Answer 38

**Bone marrow transplantation** from naturally HIV resistant people Mutation in **CCR5 coreceptor gene** meant that **CCR5** was **not expressed** and HIV could not enter new cells

Question 39

What is PrEP for HIV?

Answer 39

Pre-exposure prophylaxis Taking HIV antivirals daily to prevent possible HIV infection

Question 40

BHIVA guidelines require that people have an HIV test before going on PrEP. Why is this so important?

Answer 40

If the patient is HIV infected, treatment should be given with **three drugs** at once as **two drugs** means that **resistance** is selected **more easily**

Question 41

Single use of antiviral agents increase the risk of resistance. How is this overcome?

Answer 41

Combination therapy Antiviral resistance becomes less likely as the virus would have to have a mutation against every drug in the combination

Question 42

Describe the HIV replication cycle

Answer 42

HIV binds **CD4 receptors** and fuses with host membrane Viral RNA is converted to DNA with **reverse transcriptase**, and viral DNA is incorporated into the host nuclear DNA with **integrase** The host cell produces viral RNA and proteins, producing **immature HIV** Immature HIV is matured by **proteases** and cell budding occurs

Question 43

What are four stages of HIV replication which are targeted in combination therapy? **VIPR**

Answer 43

1. Viral entry inhibition 2. Integration of viral genome inhibition 3. Protease inhibition 4. Reverse transcriptase inhibitors

Question 44

Describe the influenza replication cycle

Answer 44

Influenza attaches via glycoproteins, whole virus **endocytosed** Virion fuses to **endosome lipids**, releasing 8 negative sense RNA segments Segments enter nucleus and **RNA-dependent RNA polymerase** produces mRNA and replicates it into new genomes

Question 45

What do viruses form in cell monolayers?

Answer 45

Plaque – as virus kills cells in the middle layer

Question 46

How can you find out how many virus particles are in a particular preparation of virus?

Answer 46

Plaque assay method Make dilutions and put them into monolayers of cells After 2/3 days, count the number of plaques formed

Question 47

What is the syncytia assay method?

Answer 47

Viruses with surface proteins that fuse at neutral pH also fuse cells together Thus helps find out how many virus particles are in a sample