Lec 19 - viral dugs Flashcards
why so hard to find viral drugs compared to bacterial
viral replication so intimately bound to host cell metabolism
must find somehting unique to virus that doesnt have parallel funciton in host
3 methods of rapid initial screening for potential viral drugs
- idnetifying anti viral compound that inhibit transcription via lac Z gene and production of beta-galactoside
- anti- virals that can inhibit memb fusion via T7 polymerase and expression of firefly luciferase
- protease inhibitors that result in lack of fluorescence seen idek how to explain it
basically, simple colour changes = good for quick screening
why antibodies not used often to bind to viral adhesin or host receptor
vry expensive
Maraviroc = HIV
- prevents entry
- by preventing interaction between CCR5 and gp120
Fuzeon = HIV
- prevents entry
- binds to gp41 and prevents the fusion event
Amantadine = influenza
- prevents uncoating
- interferes with formation of pores by the M2 protein
why was amantadine banned
- widespread resistance
- cuz only one AA change needed to be resistent to it
Pleconaril = rhinovirus
- prevents uncoating
- usually after binding to receptor, will go through conform change and lose a lipid from hydrophobic pocket
- but the drug fills this space and prevents uncoatin
How does Acyclovir prevent genome replication in herpesviridae
- first is converted to acyclo triphosphate by viral thymidine kinase and cellular kinases
- this form is a guanosine analogue
- which when incorporated into viral DNA, chain is terminated
- and importantly, host polymerase has low affinity for it
AZT - HIV , the one duesberg hates
terminates synth of growing DNA chain
- acts as thymidine analogue
- but is highly toxic, inteferes with mtDNA
- lotsa side effects
Molnupiravir - covid 19 drug - what are the 2 tautomers it can swap between
cytidine and uridine
Molnupiravir - covid 19 drug - mechanism
gets incorporated into the RNA strand and is not detected as a mutation,
as replication carries on, this can shift into either C or U
and mutations are introduced = virus cant survive
why was molnupiravir a concern
was thought to be dirivng the evolution of covid 19 strains