Antivirals Flashcards
What is AZT?
A nucleoside reverse transcriptase inhibitor.
Nucleoside analogue as OH group replaced by azide N3 group.
When given to cell –> phosphorylated by three kinases and incorporated into growing duplex.
Azido group can’t form next phosphodiester bond so becomes a chain terminator.
What is fortovase?
An inhibitor of HIV protease.
A peptide-like substrate analogue with carbonyl gp changed to OH.
Binds AS of viral protease to prevent cleavage of viral polypeptides into functional proteins found in infectious HIV.
Give some issues with influenza vaccinations.
Low efficacy in old and for certain strains e.g. H3N2 (~30%)
Effective vaccines take time to generate on scale required.
Antigenic shift (genetic reassortment of 8 gene segments).
How can influenza gain entry to a target cell?
virus binds sialylated host cell surface receptor via the glycoprotein haemaglutinin, (also responsible for the fusion of the viral envelope with the endosome membrane, after the pH has been reduced.) Then rapidly internalised before NA can cleave sialic acid.
How do the binding modes of zanamivir and tamiflu to WT neuraminase differ?
Tamiflu - conformational change in side chain of Glu276 relative to ligand-free enzyme, allowing Glu276 to be oriented away from pentyloxy group of tamiflu.
Zanamivir - H-bond formation between carboxyl gp of Glu276 and glycerol moiety of inhibitor (no change in side chain conformation required!).
What is the issue with non-nucleoside reverse transcriptase inhibitors?
Interact with allosteric site but rapid viral resistance is elicited.
What was the identity and molecular features of the initial lead compound for neuraminidase inhibitors?
NeuAc5en
O links to another carb through 3 or 6 position on galactose –> chair to half chair conformational change,
Coo- interacts with 3 Arg’s, methyl group sits in hypho pocket.
What other way can we inhibit influenza?
M2 channel ion inhibitors e.g Amantadines.
