32. Anti-viral drugs

Question 1

what is the structure of a virus?

Answer 1

nucleic acid which is either RNA or DNA. this is protected by the capsid

bigger viruses also have a lipid envelope and envelope proteins

Question 2

what is a virion?

Answer 2

a virus that is formed and active outside the host cell

Question 3

what is the difference between hepatitis B and C?

Answer 3

hepatitis B is a DNA virus, hepatitis C is an RNA virus

Question 4

outline the key features of the different types of hepatitis

Answer 4

Hep A: can only be an Acute infection (there is no need for treatment)

Hep B and C: can become chronic infections - associated with chronic inflammation at the liver –> cirrhosis and hepatocarcinoma

Question 5

how is hep b treated?

Answer 5

tenofovir (nucleotide analogue) - reverse transcriptase inhibiter, given sometimes with peginterferon alfa

Question 6

how is hep c treated?

Answer 6

• ribavirin (prevents viral RNA synthesis) and peginterferon alfa
• boceprevir (protease inhibitor)

Question 7

what do the specific drugs used and duration of treatment for hep c depend on?

Answer 7

• HCV genotype
• viral load
• past treatment experience
• degree of liver damage
• ability to tolerate the prescribed treatment
• need for liver transplant

Question 8

outline the HIV life cycle

Answer 8

1. viral proteins merge with the host cell receptors on the cell surface
2. viral membrane proteins interact with leukocyte membrane receptors –> viral capsid endocytosis
3. within the cytoplasm the reverse transcriptase enzyme converts viral RNA –> DNA
4. DNA is transported into the nucleus and is integrated into the host DNA
5. host cell’s ‘machinery’ is utilised to produce viral RNA and essential proteins
6. virus is assembled within cell –> mature virion is released out of the cell

Question 9

how does HIV attach to and enter the cell?

Answer 9

• HIV glycoprotein GP120 attaches to the CD4 receptor
• the CD40 receptors are found mainly on WBCs
• GP120 also binds to either CCR5 or CXCR4
• GP41 penetrates host cell membrane
• the viral capsid enters the cytoplasm of the cell

Question 10

what can inhibit the attachment and entry of HIV?

Answer 10

enfuvirtide - binds to HIV GP41 transmembrane glycoprotein to prevent HIV fusion

maraviroc - blocks the CCR5 receptor (found on macrophages) so the HIV capsid cannot enter the cell

Question 11

what does reverse transcriptase do?

Answer 11

converts viral single-stranded RNA –> double stranded DNA by reverse transcriptase

Question 12

what 3 things can inhibit HIV replication? give examples

Answer 12

• nucleoside reverse transcriptase inhibitors e.g. zidovudine
• nucleotide reverse transcriptase inhibitors (bind to the active site of the RT enzyme) e.g. tenofovir
• non-nucleoside RT inhibitors (bind to allosteric sites on the RT enzyme) e.g. efavirenz

Question 13

what integrates viral DNA into host DNA?

Answer 13

HIV integrase

Question 14

how is HIV integrase inhibited?

Answer 14

integrase inhibitors block the viral integrase enzyme e.g. raltegravir

Question 15

what is the role of protease enzymes in the HIV life cycle?

Answer 15

they cleave the Gag precursor protein so that the proteins become functional

Gag precursor encodes all viral structural proteins

Question 16

what is used to inhibit protease enzymes?

Answer 16

• saquinavir

- low dose ritonavir (co-administered as a booster because it reduces protease inhibitor metabolism)

Question 17

outline the virology of the herpes simplex virus

Answer 17

• ds DNA vuris
• surrounded by tegument and enclosed in a lipid bilayer
• the most common virus treated with acyclovir

Question 18

outline the tropism of the herpes virus

Answer 18

• herpes simplex virus (HSV-1) –> cold sores

- HSV-2 –> genital herpes

Question 19

how is herpes treated?

Answer 19

nucleoside analogues (like acyclovir) which block the activity of enzymes that copy DNA into RNA

Question 20

outline the virology of the influenza virus

Answer 20

• multipartite (existing as 2 or more separate particles) single stranded RNA virus
• envelope protein is neuraminidase which cleaves the sialic acid on the host cell

Question 21

outline the tropism of the influenza virus

Answer 21

nose, throat and bronchi

Question 22

how is influenza treated?

Answer 22

oseltamivir - neuraminidase inhibitor

the best way is through annual vaccination

Question 23

what is the problem with oseltamivir

Answer 23

it needs to be inhaled as soon as you are infected with the influenza virus - by the the symptoms become apparent it is too late