Antivirals - MCMP Flashcards
Describe the binding site of foscarnet on DNA polymerase.
Foscarnet binds directly to the pyrophosphate binding site on the DNA polymerase enzyme.
The pyrophosphate binding site is the location on the enzyme where pyrophosphate (a byproduct of nucleotide incorporation) is normally released during DNA synthesis.
By binding to the site, foscarnet prevents the release of pyrophosphate after a nucleotide is added to the growing DNA chain.
By blocking this release, foscarnet halts the elongation of the viral DNA strand, thus inhibiting replication.
Why are viral thymidine kinase mutants that are resistant to ganciclovir not also resistant to cidofovir or foscarnet?
Cidofovir and foscarnet do not rely on viral thymidine kinase for activation.
Why are foscarnet-resistant viruses likely to be cross-resistant to ganciclovir?
They both target DNA polymerase, so mutations in DNA polymerase will impact both of them.
How is cidofovir metabolized into the biologically active species?
It is phosphorylated by host cell kinases (opposed to viral thymidine kinase).
Why does valacyclovir have greater bioavailability than acyclovir?
The L-valyl of valacyclovir makes it more lipophilic which increases its intestinal absorption.
Which HSV drugs experience cross resistance?
- acyclovir, valacyclovir, penciclovir, famciclovir
- foscarnet, ganciclovir
Which steps in the influenza life cycle are targeted by anti-influenza drugs?
- viral release is blocked by neuraminidase inhibitors
- transcription is blocked by baloxavir
Which steps of the HBV life-cycle are inhibited by HBV drugs?
Nucleoside analogs inhibit HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, resulting in chain termination.
Which steps of the HCV life-cycle are inhibited by HCV drugs?
- Proteolytic processing for viral protein synthesis is inhibited by NS3/NS4A serine protease inhibitors
- Formation of replication complex and virion assembly are inhibited by NS5A inhibitors
- Viral RNA replication is inhibited by NS5B polymerase inhibitors
What interaction occurs between HCV protease inhibitors and cytochrome P450s?
- All NS3/4A protease inhibitors are potent CYP3A4 inhibitors and thus are associated with multiple significant drug interactions
How can HCV treatment cause HBV reactivation?
Mechanism isn’t known, but it does happen
