Antivirals

Question 1

Amantadine/rimantadine

Answer 1

Targets influenza. Block function of the M2 channel protein. Bind to high affinity site on M2 channel in pH activated state (low pH). Block Proton conduction preventing acidification of the vesicle interior and therefore preventing release of RNA genome.

Question 2

Ribavirin

Answer 2

Targets influenza virus. Taken up as guanosine analogue and phosphorylated by cellular kinases to Ribavirin MP, DP, TP. Ribavirin MP causes decrease in intracellular GTP due to inhibition of inosine MP dehydrogenase therefore inhibiting RNA/DNA synthesis. Ribavirin TP inhibits dGTP-dependent 5’-cap formation on mRNA. Also inhibits RNA polymerase. Teratogenic and causes haemolytic anaemia in 10% of patients.

Question 3

Aciclovir? Selectivity?

Answer 3

Targets herpes. Pyridine analogue. Taken up and mono phosphorylated by viral thymidine kinase. Converted to TP form by cellular enzymes. Terminates DNA strand as has 5’ c but not 3’ hydroxyl. Selective as only MP by viral thymidine kinase. 30 fold preference for viral DNA pol.

Question 4

Foscarnet

Answer 4

Targets herpes. Pyrophosphate analogue. Binds to viral DNA pol. Prevents cleavage of PPi from nucleotide triphosphate during DNA synthesis. Nephrotoxic. Administered by IV when aciclovir resistance occurs.

Question 5

How does HIV replicate?

Answer 5

Has viral reverse transcriptase that converts RNA into ds DNA. Integrated into host cell DNA by DNA integrase.

Question 6

Enfuvirtide

Answer 6

Targets HIV. Peptide based fusion inhibitor from HIV envelope glycoprotein. Binds to first heptad repeat in gp41 (HIV envelope glycoprotein) prevents pulling together of viral and mammalian membranes.

Question 7

Azidothymine

Answer 7

Targets HIV -reverse transcriptase inhibitor. Thymidine analogue. Incorporated in DNA via reverse transcriptase. Terminates DNA strand - no 3’ hydroxyl group.

Question 8

What does HIV protease do?

Answer 8

Cleaves gag proteins in functional proteins at budding from membrane or shortly after.

Question 9

Ritonavir/Saquinavir

Answer 9

Fill active site with acid resistant OH group.

Question 10

What are interferons?

Answer 10

Cytokine proteins secreted by the immune system that bind to ganglioside receptors on viral cell surface. Alpha and beta secreted by all cells. Gamma secreted by T lymphocytes and natural killer cells.

Question 11

What do interferons do?

Answer 11

Activate immune cells. Activate endonuclease that degrades viral RNA. Activate protein kinase that inhibits formation of ribosomal initiation complex.

Question 12

Zanamivir

Answer 12

Targets influenza. Analogue of N-acetylneuraminic acid so inhibits cleavage of glycoprotein during release of new viral molecules.