Lecture 17 Flashcards
Describe the different mechanisms that act as screens for inhibitors of viral proteases
Normally in a virus there are proteases that chop up into respective proteins which is needed for the virus. Medications can be designed to inhibit these.
Can analyze whether or not it was successful at inhibiting the protease through:
SDS page:
- separates protein by MW
- if you don’t see cleavage products when you use the inhibitor, it worked (successfully inhibited protease)
Beads (with fluorescence):
- bead with a protein bound to it, a cleavage site in the middle of the protein, and a fluorescent molecule on the other end
- if the fluorescence is still bound to the bead, it is insoluble (meaning protease WAS inhibited)
- if the fluorescence is cleaved, its in the soluble fraction
We are measuring to see if theres an increase in fluorescence in the soluble fraction over time = more cleavage
Why are antiviral drugs less effective against acute infections?
Antiviral drugs work by targeting specific steps in the viral replication process to stop the virus from multiplying.
However, in the case of acute infections, by the time symptoms appear and the infection is diagnosed, the virus has often already replicated significantly within the body.
This means that the peak of viral replication, when the virus is most active, has usually passed. As a result, antiviral drugs have less opportunity to effectively inhibit viral replication because much of it has already occurred. Therefore, their efficacy against acute infections tends to be limited.
What is the primary cause of symptoms in many acute viral infections?
Symptoms in acute viral infections are often caused by the immune response to the virus rather than direct tissue damage by the virus itself, a phenomenon known as immunopathology.
Many acute infections are of short duration, typically peaking in viral replication by the time symptoms manifest in the host.
How does pleconaril act?
Some viruses do not have to be endocytosed to enter the cell. The capsid can bind to a receptor on the outer membrane, make a conformational change and form a pore to feed their viral RNA through there.
Pleconaril prevents the interaction of the receptor on the outer membrane to the capsid, and therefore no pore can be formed so infection cannot occur.
How does ribavirin function?
- leads to reduced GTP pools in cells
- Inhibits RNA dependent RNA pol initiation and elongation
- Inhibits mRNA capping
Why do viruses with big genomes not have to push the cell into S phase, but small viruses do?
Because small ones need the nucleotides, DNA pols, etc so have to push the cell into S phase for this
Describe acyclovir.
What specific virus is it effective against?
- antiviral compound effective against herpes simplex virus (HSV)
Acyclovir is activated by a viral enzyme called thymidine kinase, which adds the first phosphate. Cellular enzymes then add the next two phosphates, forming acyclovir triphosphate, the active form of the drug.
Acyclovir triphosphate is selectively incorporated into replicating viral DNA by viral DNA polymerase. However, it lacks a crucial structure for DNA elongation, halting further viral DNA synthesis. This interruption in DNA replication stops viral replication, inhibiting the spread of the virus within the body.
The fact that you need a viral phosphate makes this drug VERY EFFECTIVE!! By requiring a viral enzyme, acyclovir avoids incorporation into the host cell’s DNA, reducing the risk of side effects.
What is valacyclovir?
An acyclovir derivate that is more easily taken up orally since there is a valine present on the compound (an amino acid, easier to take up orally)
Cellular enzymes later cleave the valine off so that that acyclovir is in the cell
Is hepatitis C (HCV):
enveloped or not
+ or -
dsDNA, ssDNA, dsRNA, or ssRNA
enveloped
+
ssRNA
How does Hydroxychloroquine work?
Hydroxychloroquine raises the pH of endosomes, preventing them from reaching the low pH necessary for the activation of viral glycoproteins (usually facilitate fusion, etc).
This disruption in the activation process hinders coronavirus from entering and infecting host cells effectively.
How does Nirmatrelvir function?
- oral
- Inhibits the processing of the two polyproteins required in coronavirus synthesis
- cant make proteins from this including RNA dependent RNA pol
How does Remdesivir (IV) function?
- RNA dependent RNA pol inhibitor for corona virus
- had to be administered intravenously
How does Molnupiravir function?
- Oral RNA dependent RNA pol inhibitor of coronavirus
