Non-HIV: Virus Uncoating (Su)

which drugs work via uncoating the virus

amantadine

rimantadine

When the endosomal pH reaches 5.0, the viral HA protein undergoes…

a conformational rearrangement

when the viral HA proteins undergoes conformation rearrangement it exposes a _____ on the HA

fusion peptide

when the fusion peptide is exposed on the surface of the viral HA, it leads too…

insertion into the endosomal membrane and causes fusion with the viral envelope

when HA fuses with the viral envelope via the exposed fusion peptide, the viral RNA is then….

released into the cytoplasm and transported to the nucleus where viral RNA replication can occur

what drug is this

amantadine

describe the structure of amantadine

symmetric, tricyclic primary amine used as an HCL salt

Amantadine blocks the ______of viral genome after the virus enters the cell.

uncoating

available formations of amantadine

tablet, capsule, and syrup form

how much of amantadine is excreted unchanged by the kidneys

90%

The mechanism of amantadine's antiviral activity involves interference with the viral protein called _____

ion channel Matrix-2

viral protein ion channel Matrix-2 is required for…

viral particle to be uncoated once taken inside a cell by endocytosis

the M2 protein of influenza A is _____

proton selective

M2 proteins of influenza A permits the entry of ____ into the virus particles during uncoating in the endosomes

protons

an influx of proton concentration leads to…

acidification

Acidification of the virus interior causes dissociation of the __________ from the ribonucleoprotein core a necessary step for import of the ribonucleoproteins into the nucleus.

membrane protein (M1)

dissociation of the membrane protein (M1) from the ribonucleoprotein core a necessary step for….

moving the ribonucleoproteins into the nucleus so they can replicate

T/F: Influenza A, B, C proteins all have very similar sequences

F

What viruses does amantadine cover?

influenza A ONLY

what makes amantadine able to penetrate the BBB?

cage-like structure, which enhance its lipophilicity / preclude its catabolism

amantadine is able to release ____ from storage sites

dopamine

when dopamine levels increase, it leads to an increase in _____

levodopa

amantadine delays the reuptake of ____ by nerve terminals with NMDA receptor agonistic effects.

dopamine

T/F: Amantadine can relieve Parkinsons disease

T

high doses of amantadine can lead to what ADE

depression, dizziness, urine retention, hallucination, headache & anxiety. GI side effects –nausea, diarrhea, constipation, anorexia

what drug is this

rimantadine

_____ is a branched homologue of amantadine, synthetic adamantane derivative.

rimantadine

Rimantadine is _____ effective against influenza A virus, versus amantadine and shows ____CNS side effects.

more; less

ADE of rimantadine

CNS, GIT

how much of rimantadine is excreted unchanged

20%

T/F: amantadine is metabolized in the body

F

rimantadine is metabolized in the ____ after oral dosing

liver

rimantadine major metabolite

hydroxylated derivatives