Pharmaceutical chemistry of antiviral drugs

Question 1

which drug is a competitive inhibitor of the natural nucleoside

Answer 1

Nucleoside inhibitors - binds to orthosteric site

Question 2

which drug is a non - competitive inhibitor of viral synthesis?

Answer 2

Non-nucleoside inhibitors bind to allosteric site

Question 3

how does metabolic activation occur?

Answer 3

inactive nucleoside inhibitors are activated by kinases - getting phosphorylated to become active

Question 4

what causes chain termination

Answer 4

lack of OH group of 3’ so no phosphodiester bond can form to carry on transcription

Question 4

what phosphorylates the first step of acyclovir to be more selective?

Answer 4

Viral TK is 100 times more effective for converting acyclovir than the host TK in the slowest conversion step

Question 5

what is the ProTide approach?

Answer 5

covering of negative charge to allow the antiviral drug to cross the cell membrane.

Requirements:
lipophilic
stability in plasma
hydrolysis in cells
by-products not toxic

Question 6

examples of protide blocking groups

Answer 6

pheny and 1-naphthyl
amino acid motif + short linear R group to protect COOH

Question 7

adv of protide approach

Answer 7

• skips Rate limiting step
• gives non - toxic by - products