Pathogenicity of infection--> influenza III Flashcards
When does influenza result in a pandemic w/ high mortality rates?
After antigenic shift
Why is there no background immunity to an antigenically shifted virus?
Completely diff surface proteins to things weve seen before
Main option for disease management in a pandemic?
Drugs
Anti influenza drug classes?
M2 inhibitors, Neuraminidase inhibitors
M2 inhibitors?
Amantadine, Rimantadine
Neuraminidase inhibitors?
Oseltamivir, zanamivir
How do M2 inhibitors work?
Block the ion channel, stops protons from entering the virus and thus reduces the virus’ ability to uncoat and release viral RNA
How do neuraminidase inhibitors work?
Block NA–> cant cleave the sialic acid receptor–> new viral particles remain attached to the affected cell so cant infect other cells
What do the neuraminidase inhibitors look similar to?
Sialic acid
What type of inhibitors are the NA inhibitors?
Competitive–> they bind to the NA active site instead of sialic acid
Advantage of NA inhibitirs?
Active against all strains of influenza and all serotypes
What is looked for when developing a competitive inhibitor?
Make a molecule that resembles the transition state of the chemical process being carried out by the enzyme
First molecule made in NA inhibitor development?
DANA–> had a flat ring like sialic acid in the transition state
DANA binding ability to NA compared to sialic acid?
1000* better than sialic acid
How was crystallography used in NA inhibitor development?
Could see where the sialic acid was sitting in the NA and what proteins it was interacting with, so knew where to target
Main observations fro crystallography of NA and DANA?
OH group formed hydrogen binding w/ glutamic acid in the active site
Large empty pocket in the influenza NA
What was modified about DANA after the crystallography findings?
Put a guanadino group instead of the OH group–> converted the H bond to a stronger ionic bond
New drug potency compared to DANA?
1000* more potent than dana
Relenza administration?
Cant be orally administered–> taken by inhalation using a dry powder and an inhaler
Benefit of administering relenza via inhalation?
Directly to the site of infection
Zanamivir half life?
2.5 hrs in serum
Zanamivir effect?
Normal influenza–> reduce symptom duration by one day if administered within 48 hrs of symptoms
Pandemic-> life saving therapy
