Anti Virals

Question 1

Viral physiology: summarise how viruses use the host cell to replicate

Anti-viral drugs: summarise the mechanisms of action of anti-viral drugs used in the treatment of HIV, hepatitis, herpes and influenza

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

Summarise the mechanisms of action of antiretroviral drugs

Describe the actions of other antiviral drugs

Answer 1

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Question 2

Describe the general structure of the virus

Answer 2

• contains genetic material = RNA / DNA
• -> within a capsid
• which is then encapsulated by lipid envelope
• on lipid envelope layer, there are envelope proteins projecting out

Question 3

Describe drugs used to treat Viral Hepatitis:

a) Tropism
b) Hep B
c) Hep C

Answer 3

–> only chronic infections require treatment

a) Tropism

b) Hep B
- Tenofovir
- -> Nucelotide analogue
- -> given sometimes with + peginterferon alfa

c) Hep C
- Ribavirin + peginterferon alfa
- -> Ribavirin = nucleoside analogue
- -> prevents viral RNA synthesis

• Boceprevir
• -> protease inhibitor
• -> Most effective against Hep C genotype 1

Question 4

Describe the HIV life cycle

Answer 4

1. Attachment & Entry
   - -> Viral membrane proteins interact with leukocyte membrane receptors
   - -> Viral capsid endocytosis

HIV Glycoprotein (GP)120 attaches to CD4 receptor

• GP120 also binds to either CCR5 or CXCR4
• GP41 penetrates host cell membrane & viral capsid enters

2. Replication & Integration
   - -> Within cytoplasm - reverse transciptase enzyme converts viral RNA –> DNA
   - -> DNA transported into nucleus & integrated into host DNA

replication = Viral single-stranded RNA –> double stranded DNA by reverse transcriptase

Integration = Viral integrase inserts viral DNA into host DNA

3. Assembly & Release
   - -> Host cell’s ‘machinery’ utilised to produce viral RNA & essential proteins
   - -> Virus is assembled within cell –> mature virion is released

Gag precursor –> encodes all viral structural proteins
HIV protease cleaves Gag precursor protein

Question 5

For HIV Entry Inhibitors, how do antiretrovirals target the process of attachment and entry?

Answer 5

a) Enfuvirtide
- Binds to HIV GP41 transmembrane glycoprotein
(attachment inhibitor)

b) Maraviroc
- Blocks CCR5 chemokine receptor (core receptor of HIV)

Question 6

For HIV replication inhibitors, how do retrovirals target the process of HIV replication ?

Answer 6

a) Nucleoside RT inhibitors
Activated by 3 step phosphorylation process
E.g. Zidovudine

b) Nucleotide RT inhibitors
Fewer phosphorylation steps required
E.g. Tenofovir

c) Non-nucleoside RT inhibitors
No phosphorylation required
Not incorporated into viral DNA
E.g. Efavirenz

Question 7

For HIV integrase inhibitors, how do retrovirals target the process of HIV integration ?

Answer 7

a) Integrase inhibitors

e. g Raltegravir

Question 8

For HIV protease inhibitors, how do retrovirals target the process of HIV Assembly + release ?

Answer 8

Protease inhibitors (PI)
= e.g Saquinavir 

–> Low dose Ritonavir reduces PI metabolism –> co-administered as ‘booster’

ADV = no transmission of HIV through unprotected sex

Question 9

Describe the Herpes Simplex Virus

Answer 9

• double stranded DNA virus
• enclosed in a lipid bilayer

2 types
HSV 1 –> cold sore
HSV 2 –> genital herpes

Question 10

Influenza

Answer 10

• single stranded RNA Virus

- envelope protein neuraminidase –> releases virus –> allows transmission

Question 11

SUMMARY 1
Distinguish between different types of virus and describe how they use the host cell to replicate

a) HIV - Retrovirus, leukocytes

b) Hepatitis - DNA & RNA
viruses, hepatocytes

c) Herpes Simplex - DNA virus
d) Influenza - RNA virus

Answer 11

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Question 12

SUMMARY 2
Summarise the mechanisms of action of antiretroviral drugs

a) Entry inhibitors - Enfuvirtide & Maraviroc
b) RT inhibitors - Nucleoside analogues (Zidovudine), Non-nucleoside analogues (Efavirenz)
c) Integrase inhibitors - Raltegravir
d) Protease inhibitors - Saquinavir

Answer 12

-

Question 13

What are the treatment methods of HSV ?

Answer 13

Nucleoside analogues –> Aciclovir

Question 14

What are the treatment methods of Influenza ?

Answer 14

Neuraminidase inhibitor –> Oseltamivir

effective = VACCINE