MOA of viruses Flashcards
compare the virus and host targeting antiviral approaches, analysing pros and cons
virus target e.g. HCV - nucleotide inhibitor class (inhibition of the viral polymerase)
adv - potential selective toxicity towards the virus and reduced toxicity.
disadv - risk of developing drug resistance
Cell-host target e.g. HIV - targets human CCR5 protein (blocking viral entry)
adv - reduced risk of drug resistance and targets multiple viruses
disadv - reduced specificity
Outline the main MOA and targets of the different classes of antiviral drugs
1- viral attachment
2-viral penetration
3-viral uncoating
4-viral genome replication and transcription
4b-viral DNA integration
5-protein synthesis and processing
6-viral budding
HIV entry mechanism
HIV gp120 proteins bind to CD4 receptor on T-immune cells.
CD4 binding -> enables gp120 to interact with a coreceptor protein of the host cell.
Virus target of HIV
Fostemsavir
targets the HIV gp120
prevents its binding to CD4 cellular receptor
cell host target of HIV
Maraviroc
CCR5 antagonist
prevents the HIV-1 gp120/CCR5 interaction
How does HIV fusion step work
coreceptor binding induces insertion of gp41 fusion peptide into the cell membrane
this promotes fusion between viral envelope and host membranes
what drug prevents HIV fusion step
Enfuvirtide - mimics components of the HIV-1 fusion machinery binding to gp41, preventing fusion of envelope and membrane
How do viral coating inhibitors work and give an example
-bind and block the M2 channel lumen - preventing virus uncoating
-M2 blockers e.g. Amantadine
How do viral polymerase inhibitors work?
Nucleoside analogues - contain modifications to stop or impair synthesis of nucleic acids (selective for viral polymerases). Hijack polymerase elongation and require activation by host kinases.
Non - nucleoside HIV - do not resemble natural nucleotides. Bind to allosteric site, not incorporated into nucleic acid chain. Indirectly inhibit its function and doesn’t need activation steps.
How do integrase inhibitors of HIV work
e.g. Raltegravir - block the strand transfer step of HIV DNA integration by chelating the Mg2+ in the active site
how do viral protease inhibitors work
selectively bind to viral proteases stronger than natural substrate. peptidomimetics –> contain non - cleavable groups to block their active site. Inhibiting precursors into key proteins
how do viral release inhibitors work
bind to neuraminidase and block the active site - preventing the release and spread of viral progenies
