35 - hepatitus C ii

Question 1

what is sofobuvir. how does it go from a prodrug to an active drug, and what technique does of inhibition does the active drug employ

Answer 1

• Prodrug
  
  • black part gets cut off by metabolism and then metabolism adds some phosphates to the drug
• Active drug is a chain terminator
  
  • targets viral polymerase. blocks the replication of viral nucleic acid by the mechanism of chain termination

Question 2

describe how chain termination is employed by the active form of sofobuvir

Answer 2

• here they left the OH, but made it non-nucleophilic, restricted the electron donating ability of the 3’ OH
  
  • first thing they did was add a F next to the OH, and it acts as an EWG → draws electrons away from the OH. makes OH a less good nucleophile by inductive effect
  • second thing they did was adding a methyl group next to the F. it generates a steric congestion near the nucleophile. creates a large nucleophile, reduces the OH’s electron donating ability

Question 3

what is ledipasvir and how does it inhibit viral enzyme formation

Answer 3

• Ledipasvir
  
  • Sticks to the small protein
    
    • drug sticks to small protein, so A cannot stick to B because the drug is in the way, this prevents the formation of that special enzyme, prevents the enzyme from replicating
  • Prevents protein association and formation of viral enzyme
• Virus contains an enzyme which is formed from more than one protein
  
  • virus is formed by two proteins which have to stick together to make the operation enzyme (quaternary)
  • on the enzymes, one of the proteins is really big and the other is really small → makes a functional enzyme
• Large protein must bind to a small protein to form a functional enzyme

Question 4

what is harvoni, when was is approved and what is so good about it

Answer 4

• Approved in 2014
  
  • first example of a small molecule drug that is able to cure a viral infection.
• Combination of Ledipasvir and Sofobuvir
  
  • ledipasvir is drug that prevents the formation of the quaternary structure
  • sofobuvir is a chain termination drug
• Capable of curing HCV infection in 8 to 24 weeks
  
  • only thing that can cure the infection by itself