MD6: Development of Neuraminidase Inhibitors

Question 1

what is genetic shuffling (reassortment)

Answer 1

entire genes encoding a different H or N sub-types is incorporated into the ‘new’ virus
often occurs in animal hosts which are co-infected with two or more strains of influenza

Question 2

what is the antigenic shift of pandemic influenza

Answer 2

occurs when a new strain of virus is formed, often originating from another species
no immune history so no natural protection, impossible to predict the nature of the strain or when it will emerge
can be highly pathogenic and results in high rate of mortality
cannot be predicted

Question 3

what are the two groups of influenza therapeutics

Answer 3

adamantanes (M2 inhibitors), neuraminidase inhibitors

Question 4

what are two examples of adamantanes (M2 inhibitors)

Answer 4

amantadine, rimantadine

Question 5

what are two examples of neuraminidase inhibitors

Answer 5

oseltamivir, zanamivir

Question 6

how do adamantanes work

Answer 6

interfere with the function of the transmembrane domain of the M2 protein of influenza A viruses
decrease the release of influenza A viral particles into the host cell

Question 7

how is amantadine used

Answer 7

reduce duration of illness, orally administered, activity against influenza A virus only, through inhibiting replication
has comparable antiviral and clinical activities when used for prophylaxis or treatment

Question 8

what are the problems with amantadine

Answer 8

rapid development of resistance to amantadine in 30% of treated patients
wide range of side effects and toxicity

Question 9

how is rimantadine used

Answer 9

less toxic alternative to amantadine, structurally similar

similar mechanism of action to amantadine and suffers from many of the same problems

Question 10

what are the advantages of neuraminidase inhibitors

Answer 10

active against all strains of influenza (A,B,C) and all stereotypes

Question 11

what is zanamivir

Answer 11

introduction of guanadino group
results in selective influenza neuraminidase over human as it fits better, guanadino group formed a hydrogen bond with glutamate amino acid
potency of the compound improved
reduces duration of illness by one day if administered within 48hours of onset of symptoms

Question 12

what is oseltamivir

Answer 12

based on relenza, but modifications were made to improve oral bioavailability
removed guanadino group to improve lipophilicity
removed oxygen ring to improve stability, allowed double bond to be moved
reduces duration of illness by one day if administered within 48 hours of symptoms