FINAL L3 - Innovation in Antiviral Drugs

Question 1

Viread (Tenofovir)

Answer 1

Relisten for importance and structure**

Question 2

Hepatitis C viral Lifecycle

Answer 2

-Virus entry
-Fusion and uncoating
-Translation into polyprotein
-Cleavage of polyprotein
-Formation of membrane bound replication complex
-Replication
-Virion packaging and assembly
-Virion maturation and release

Question 3

Activation of Sofosubuvir

Answer 3

Turns into active triphosphate (GS-461203) or different GS’s (GS-696965; GS-331007)

Question 4

Costs of untreated hepatitis:

Answer 4

$24,000 - patient with hep C
$60,000 - patient with end stage liver disease
$112,000 - Liver cancer
-$500,000 - liver transplant

Question 5

Avoided conditions related to Hep C

Answer 5

Liver related deaths - 126,500
Advanced cirrhosis - 124,200
Liver cancer - 78,800
Liver transplants - 9,900

Question 6

Paxlovid and Molnupriavir

Answer 6

Pictures and Relisten (slide 30)

Question 7

T/F: Antiviral drugs are typically very insoluble

Answer 7

True

Question 8

Prodrug solutions

Answer 8

A prodrug can be defined as a drug substance that is inactive in the intended pharmacological actions and must be converted into the pharmacologically active agent by metabolic or physico-chemical transformation

Question 9

Antiviral drug solubility formulation

Answer 9

-Melt Extrusion
-Spray Drying

Question 10

Prodrug example

Answer 10

Sofosbuvir - It is converted to the triphosphate and inhibits the NS5B polymerase

Question 11

Antiviral drugs are typically…

Answer 11

Poorly soluble and have poor bioavailability

Question 12

One way to improve solubility and bioavailability is to

Answer 12

Make an amorphous dosage form by melt extrusion (API and Matrix polymer go in, melt, mix, have homogeneous dispersion, and leave through a cooling chamber)