antivirals and vaccines Flashcards
what do antivirals do
Block specific steps in the virus life cycle
what is important for antivirals to be used in people
Active aginst virus replication, but not normal cellular function to reduce toxicity
how does antivirals target
Exploit strucutural, functional, and genomic information
How common is viral resistance to antiviral drugs
common, requiring continued development efforts
general ways that antivirals can block viruses
Fusion inhibitors Ion channel blockers Polymerase inhibitors Protease inhibitors Neuramidase inhibitors
What does Enfuvirdtide treat
HIV
action of Enfuvirtide
Blocks refolding of gp41
by blinding to it, iInhibiting membrane fusion
what does Amantadine and rimantadine treat
influenza
how does amantadine and remantadine work
blocks influenza ion channel (M2) (brings in H+ normally, so blocked, endsome can’t become acidified) preventing nucleocapside release at the end of the cell entry process
action of nucleoside analogs
Chain terminators- lack some portion of the sugar ring(missing one of the hydroxyl groups)
what does Acyclovir treat
herpesvirus infection
the first antiviral approved for clinical use
Acyclovir
what were the key hurdles for antiviral success of Acyclovir
Specificity depending on virus thymadine kinase (TK)-binds here
Bioavailability-hard to get to the site of infection
what is Acyclovir most effective against
HSV-1 and HSV2
less effective for EBV and VZV and even less effective for CMV
what is Acyclovir
like nucleoside inhibitors for herpesvirus infections
what is Ganciclovir effective against
CMV
why is Ganciclovir more toxic than other antiviral preventing genome replication
interference with Cellular kinase
Benifit of Valganciclovir over acyclovir
SImilar activtiy, but improved oral bioavailability
what does Foscarnet treat
HErpesvirus
how does Foscarnet treat herpesvirus
Prevents viral polymerase activity
how is Foscarnet administared
IV
problem with Foscarnet
Toxic
what can inhibit HIV and HBV
Nucleoside inhibitors
why are nucleoside inhibitors good for HIV and HBV
Good oral availability
problem with Nucleosides inhibitors for HIV and HBV
toxicity
Resistance observed
how to use nucleoside inhibitors for HIV and HBV
use more than one type of nucleoside inhibitors, including one from another class
can you use nucleoside inhibitors on RNA viruses
Yes
what does Ribavirin treat
RNA viruses
Action of triphosphate form Ribavirin to treat RNA viruses
TRiphophate form inhibits polymerase
action of monophosphate form Ribavirin to treat RNA viruses
Inhibits inosine monophosphate deydrogenase lowering GTP in cells
what does Ribavirin do generally to treat RNA viruses
Impairs capping of mRNA
what is needed for maturation of progeny viruses
cleavage of virus polypeptide
are immature progeny(un-cleaved polypeptide) infectious
no
What does ritonavir treat
HIV
action of ritonavir
Blocks cleavage of GAg-POl polypeptide
Boosts activity of other protease inhibitors beacuse it also blocks the action of cellular proteases that act on other viral protease inhibitors
what is needed to influenza to be released by the cells
Neuraminidase
Neuraminidase inhibitors do what
keep influenza from leaving the cell
what is all part of bioavailability
absorption into the body transport to site of infection intake by cell therapeutic window (half-life)
antiviral challenges
Bioavailability
Specificity
Toxicity
what antivirals block viral attachment and entry
enfuviritide (HIV)
Docosanol (HSV)
Palivizumab (RSV)
what antivirals block penetration
Interferon-alpha (HBV, HCV)
what antivirals block uncoating
Amantadine (influenza)
Rimantadine (influenza)
what antivirals block nucleic acid synthesis
NRTI (HIV) NNRTI (HIV) Acyclovir (HSV) toscarnet (CMV) entecavir (HBV)
What antivirals block late protein synthesis and preocessing
Protease inhibitors (HIV)
what antivirals block viral release
Neuraminidase inhibitors (Influenza)
how were interferons discovered
By isaacs and Lindenmann, noticing that cultured cels infected with 1 virus were resistant to infection by a second virus.
This was transferable to uninfected cels
Identified proteins responsible for the effect
mech of interferon action
Not well understood
do Interferons work better against RNA or DNA virus
RNA virus
what is reversion of the poliovaccine
Vaccine-acquired paralytic poliomyelitis
what amount of poliovaccines revert
1:1,000.000 to 3,000,000
what poliovaccine is now used in the US
killed vaccine because polio rate is so low
what cell types are important for vaccines
B cells
CD8+ T cells
CD4- T cells
what vaccines utilize B cells only
Pneumonococccal
HIB (unless conjugated to other antigens)
what vaccines utilize B cells and T cell immunity including sec IgA
Influenza, polio, oral typhoid
