Antivirals

Question 1

List some structural features of a virus.

Answer 1

Envelope proteins.
Lipid envelope.
Capsid (protein shell surrounding the genetic material of the virus).
Genetic material (RNA and DNA).

Question 2

How is hepatitis C treated?

Answer 2

Ribavirin and peginterferon alpha.
Ribavirin → nucleoside analogue prevents viral RNA synthesis.
Boceprevir → protease inhibitor, most effective against hepatitis C genotype 1.

Question 3

How is hepatitis B treated?

Answer 3

Tenofovir → nucleotide analogue, given sometimes with peginterferon alpha.

Question 4

What is the tropism of viral hepatitis?

Answer 4

Liver hepatocytes.

Question 5

What is the goal of hepatitis C treatment?

Answer 5

The goal of HCV treatment today is to cure the virus.

Combination of drugs.

Question 6

What do the specific drugs and duration of treatment of hepatitis C depend on?

Answer 6

HCV genotype (genetic structure of the virus).
Viral load.
Past treatment experience.
Degree of liver damage.
Ability to tolerate the prescribe treatment.
Need for liver transplant.

Question 7

What are the stages in the life cycle of HIV?

Answer 7

Attachment and entry.
Replication and integration.
Assembly and release.

Question 8

What happens in the attachment and entry stage of the HIV life cycle?

Answer 8

Viral membrane proteins interact with leukocyte membrane receptors.
Viral capsid endocytosis.

Question 9

What happens in the replication and integration phase of the HIV life cycle?

Answer 9

Within cytoplasm- reverse transcriptase enzyme converts viral RNA to DNA.
DNA transported into nucleus and integrates into host DNA.

Question 10

What happens in the assembly and release phase of the HIV life cycle?

Answer 10

Host cell’s machinery utilised to produce viral RNA and essential proteins.
Virus is assembled within cell, and the mature vision is released.

Question 11

List some HIV entry inhibitors.

Answer 11

HIV glycoprotein (GP) 120 attaches to CD4 receptor.
GP120 also binds to either CCR5 or CXCR4.
GP41 penetrates host cell membrane and viral capsid enters.
Enfuvirtide: binds to HIV GP41 transmembrane glycoprotein.
Maraviroc: blocks CCR5 chemokine receptor.

Question 12

List some HIV replication inhibitors.

Answer 12

Reverse transcription: viral single-stranded RNA → double-stranded DNA by reverse transcriptase.
Nucleoside RT inhibitors: activated by 3 step phosphorylation process, e.g. zidovudine.
Nucleotide RT inhibitors: fewer phosphorylation steps required, e.g. tenofovir.
Non-nucleoside RT inhibitors: no phosphorylation required, not incorporated into viral DNA, e.g. efavirenz.

Question 13

What is DNA integration in HIV?

Answer 13

Viral integrase inserts viral DNA into host DNA.

Question 14

Give an HIV integrase inhibitor.

Answer 14

Raltegravir.

Question 15

List HIV protease inhibitors.

Answer 15

In the assembly and release phase, Gag precursor encodes all viral structural proteins and HIV protease cleaves Gag precursor protein.
Saquinavir- 1st generation protease inhibitor.
Low dose ritonavir- reduces protease inhibitor metabolism, coadministered as ‘booster’.

Question 16

What does raltegravir do?

Answer 16

Inhibits viral integrase.

Question 17

List viral capsid proteins.

Answer 17

HIV GP41- enfuviritide prevents HIV fusion and entry.
Macrophage CCR5 receptor- maraviroc inhibits CCR5 receptor.
Influenza neuraminidase.

Question 18

What can nucleoside analogues be used to treat?

Answer 18

HIV
Hepatitis
Herpes simplex

Question 19

How can nucleoside analogues be used to treat HIV?

Answer 19

Nucleoside (e.g. zidovudine) and nucleotide reverse transcriptase inhibitors bind to active site of enzyme.
Efavirenz- non-nucleoside binds to allosteric site on reverse transcriptase enzyme.

Question 20

What nucleoside analogue can be used to treat hepatitis B?

Answer 20

Tenofovir (reverse transcriptase inhibitor).

Question 21

What nucleoside analogue can be used to treat hepatitis C?

Answer 21

Ribavarin (purine analogue).

Question 22

What is the virology of the herpes simplex virus?

Answer 22

Double-stranded DNA.

Surrounded by tegument and enclosed in a lipid bilayer.

Question 23

What is the tropism of the herpes simplex virus?

Answer 23

Herpes simplex virus (HSV)-1 → cold sores.

HSV-2 → genital herpes.

Question 24

How is herpes simplex virus treated?

Answer 24

Nucleoside analogues, e.g. acyclovir.

Question 25

What is the virology of influenza?

Answer 25

Multipartite single stranded RNA virus.

Envelope protein neuraminidase, leading to release.

Question 26

What is the tropism of influenza?

Answer 26

Nose, throat and bronchi.

Question 27

What is the treatment of influenza?

Answer 27

Neuraminidase inhibitor, e.g. oseltamivir.

Question 28

Distinguish between different types of virus and describe how they use the host cell to replicate.

Answer 28

HIV: retrovirus, leukocytes.
Hepatitis: DNA and RNA viruses, hepatocytes.
Herpes simplex: DNA virus.
Influenza: RNA virus.

Question 29

Summarise the mechanisms of action of antiretroviral drugs.

Answer 29

Entry inhibitors: enfuviritide and maraviroc.
Reverse transcriptase inhibitors: nucleoside analogues (zidovudine), non-nucleoside analogues (efavirenz).
Integrase inhibitors: raltegravir.
Protease inhibitors: saquinavir.

Question 30

Describe the actions of other antiviral drugs.

Answer 30

Nucleotide analogues: ribavirin, acyclovir.
Protease inhibitors: boceprevir.
Neuraminidase inhibitors: oseltamivir.