AV Flashcards
influenza Vaccine
best !
Zanamivir
Influenza neuroaminidase inhibitor
active drug
analogue of N-acetylneuraminic acid
used at early stages of infection
inhibit viral aggregation
release from cell
movement through upper respiratory tract
Oseltamivir
flu NA inhibitor ethyl ester pro-drug analogue of N-acetylneuraminic acid used at early stages of infection
inhibit viral aggregation
release from cell
movement through upper respiratory tract
Ribavirin
Hepatitis C
Flu
inhibits viral RNA dependent RNA polymerase
guanosine analogue take up
phosphorylated by cellular kinases to MP, DP, TP
MP = decrease GTP - inhibits inosine monophosphate dehydrogenase, hence DNA/RNA synthesis.
TP inhibits dGTP dependent 5’Cap formation on mRNA. mimick the cap to inhibit eIFE
bind the nucleotide binding site of viral RNA polymerase - inhibits initiation and elongation of viral mRNA
terogenic - causes haemolytic anaemia in up to 10% of patients - drug accumulation in RBCs
antiherpes
simplex + zoster active
all available ones target virally encoded DNA polymerase that replicate dsDNA genome.
viral DNA polymerase in same way as mammalian DNA polymerase.
Acyclovir
anti - herpes pro drug
specific purine analogue
lack cyclic sugar of 2’ deoxyguanosine
need viral thymidine kinase
then to acyclovir - TP by cellular enzymes
30 x more potent interaction with viral DNA Pol
competitive substrate
incoorperated and cause termination of DNA replication
uses of acyclovir
topicaly, oral, IV
cidofovir
herpes
pyrimidine analogue
nucleoside phosphonate analogue of cytosine
converted to diphosphoryl derivative by cellular enzymes
selectively inhibit DNA pol of CMV
incorporates itself into viral DNA
for CMV retinitis
MORE TOXIC - TOPICAL USE
side effects: nephrotoxicity, nausea, hair loss, vomiting etc
Trifluridine -
Idoxuridine
herpes
cytosine analogues
TOXIC
Trifluridine - does not require activation by TK , inhibits mammalian DNA pol too
Idoxuridine - inhibits viral DNA polymerase, requires viral TK
Foscarnet -
herpes
organic analogue of pyrophosphate
bind DNA Pol of CMV
selective but does not require IC metabolism
prevents cleavage of PPi from NTP during DNA synthesis
nephrotoxic proteinuria
IV
when acyclovir resistance occurs
however alterations in viral DNA pol may give resistance
HIV
two copies of single stranded RNA genome
reverse transcriptase - poor fidelity
aspartic acid protease - cleaves polyprotein ie Gag
RT inhibitors
HIV
non nucleoside reverse transcriptase inhibitors NNRTIs
NRTIs
nevirapine
NNRTI
HIV
used to prevent mother to child spread
bind hydrophobic pocket in the subdomain of p66 which is about 10 angstrom away from the active site (known as the NNRTI pocket)
AZT / zidovudine / azidothymidine
thymidine analogue
NRTI
lack 3’OH as replaced by non functional azido group (N3)
chain terminator
co - admin with hydroxyurea - decreases thymidine concentration - potentiates effects
Valyl ester - increases bioavailability - makes resemble peptide to utilise the non-selective peptide transporters in gut. ester bond cleaved in plasma ( used on other drugs too )
Amantadine
Rimantadine
FLU
targets M2 - prevent proton conductance.
2 mechanisms of binding
x-ray crystallography - bind to high affinity open state at low pH ( perhaps due to absence of pl bilayer)
NMR - show bind to low affinity closed state
prevent the acidification of intervir of virion needed for fusion of endosome and viral capsule membranes
