Clinical use of antiviral drugs Flashcards
why is it difficult to develop safe antivirals,
are intracellular parasites .’. hard to make antivirals that kill virus and not host
viruses have high mutation rate inside host .’. produce quasispecies .’. may become resistant
can become latent/hidden in the body
can integrate into our own chromosome so v difficult to get rid of (e.g. HIV)
so how do we selectively target viruses
antivirals specifically target virally produced enzymes (different to human .’. can be selectively targeted)
e.g. thymidine kinase (herpes) protease (HIV) reverse transcriptase (HIV) dna polymerase (HBV)
what do we use antivirals for
treat acute and chronic infections, post exposure prophylaxis, preexposure prophylaxis
antivirals and timescale of administering
needs to be administered soon after infection.
incapable of eradicating latent infections
antivirals against herpes virus
aciclovir, ganciclover
Valaciclovir and Valganciclovir
what is aciclover
effective and safe antiviral bc selective action. for herpes simplex. HSV thymidine kinase has 100x greater affinity for aciclover than our own phosphokinases
how is aciclover so selective
enters cells and gets phosphorylated by HSV thymidine kinase. once phosphorylated 3x = highly polar .’. cannot enter/leave cells
.’. only in cells that it is phosphorylated does its effects occur. in human unaffected cells unlikely to be phosphorylated so just moves back out off the cell
mechanism of aciclover
analogue of guanine .’. once phosphoryalated= compete w/ dGTP for DNA polymerase.’. incorporated into the viral DNA blocking addition of GTP.
Aciclovir triphosphate =chain terminator and prevents the addition of anymore DNA .’.stops viral replication
.’. infected cells die
when do we use ganciclovir
- > Treatment of CMV reactivation that can occur in organ transplant recipients
- > Treatment of congenital infection in newborns
- > Prophylaxis in organ transplant recipients
