Oseltamivir Flashcards
What is flu? What are the symptoms?
Highly contagious acute viral infection that affects people of all ages. Fever, coughing, sore throat, chills, muscle pains, fatigue, headache
Why are vaccines only affective for a few years?
The influenza virus mutates very quickly
How many strains does the WHO predict will be in widest circulation each year?
3 or 4
How long is needed to formulate and produce the vaccine on a large scale?
6 months
What is a pandemic?
Prevalent throughout an entire country, continent or the whole world
What does zoonotic mean?
Transferred between species
What are the two proteins on the extracellular side of the virus?
Haemagglutinin and neurominic acid
What are the first two steps in the viral replication cycle?
There is binding to the target cell and endocytosis
What is the step after endocytosis?
proton channels allow protons to enter for lowering the pH for rupture
What does the viral DNA do?
Hijack’s the cell’s replication machinery to make copies of itself
What happens after replication?
There is assembly of components, budding and release of the virus.
What do M2 ion channel protein inhibitors do?
Block the proton channel so no protons move into the vesicle containing the virus
Why aren’t the M2 ion channel protein inhibitors used any more?
The influenza virus is immune to them now, they had off target effects in the CNS.
Explain one theory of how Ribavirin works.
It’s carboxamide group can make the native nucleoside drug resemble adenosine or guanine so when it is incorporated into the DNA it pairs with uracil or cytosine. This causes mutations in DNA dependent replication. The hypermutation can disrupt the viral replication cycle.
What does neuraminidase normally do to the haemagglutinin attached to the cell?
Cleaves it
What does haemaglutinin receptors on the cell contain?
Sialic acid
What happens normally after neuraminidase cleaves the haemaglutinin from the cell?
There is release of new virons
What happens when a neuraminidase inhibitor is present?
The neuraminidase can’t cleave the linkage so the viral particle is bound to the cell surface so no viron release
What is the overall effect of neuraminidase inhibitors?
They slow the viral progression and replication
What are the two neuraminidase inhibitors?
zanamivir and oseltamivir
What are the neuraminidase inhibitors very similar to?
The natural product (neuraminic acid/sialic acid)
What does successful binding of oseltamivir require?
Glu276 to reorientate itself
What is the natural substrate of neuraminidase?
Neu5Ac
What confers resistance to oseltamivir?
A single mutation (His110Tyr) which prevents Glu276 from reorienting.
What are the two latest developments?
Peramivir and Laninamivir
What is exciting about Peramivir?
It got full drug approval in 2014.
What is Laninamivir related to?
Replace Zanamivir
Where and when was laninamivir approved?
Japan, 2010
