Antiviral Drugs Flashcards
The most severe constraint limiting the use of antiviral drugs?
not the lack of efficacy but the toxicity to the mammalian cell (poor selective toxicity)
Virus specific enzymes
proteases, mRNA capping enzyme, neuraminidases, ribonucleases, kinases, integrases and uncoating enzymes
In the case of antivirals, the therapeutic window is
the ratio of the minimum dose that is toxic to host cells over the minimum dose that is toxic to the virus
What is required to maintain the suppression of many viral infections
an intact immune system (because antiviral drugs available so far are virostatic)
Three subclasses of drugs that prevent viral entry into host cells
- inhibitors of attachment that compete with a viral receptor
- coreceptor antagonists
- fusion inhibitors that prevent fusion with host cells
Maraviroc
CCR5 coreceptor antagonist - tested for AIDS treatment
what kind of patients should maraviroc be used in
CCR5-tropic patients (M-tropic)
When should maraviroc dose be adjusted
if used with drugs that inhibit or stimulate cytochrome P450 CYPA3 enzyme to adjust for changes in its metabolism
cenicriviroc
dual CCR5 and CCR2 antagonist
PRO 140
a CCR5 monoclonal antibody
for treatment experienced patients
Enfuvirtide (T-20)
fusion inhibitor
derived from the natural gp41 HR2 sequence
first HIV fusion inhibitor acting by specifically inhibiting the function of the gp41 transmembrane glycoprotein of HIV-1
Virus uncoating corresponds to
loss of viral protein coat (nucleocapsid proteins in nonenveloped viruses) or fusion of viral lipid memebranes (loss of lipid envelope in membrane containing viruses) with an endosome/lysosome
good target for therapy by interfering with pH?
endosome/lysosome compartment
Arildone
inhibits uncoating of picornaviruses that do not have a lipid membrane by blocking ion transport; drug inserts into a canyon in the VP1 viral proteins and blocks ion transport
What happens when you inhibit viral integrase?
prevent the insertion of the virus genetic code into the DNA of infected cells
Integrase inhibitors
Raltegravir (1st one)
elvitegravir, dolutegravir ect.
targets of drugs that act on the duplication of the viral genome
polymerases
nucleoside analog drugs
idoxuridine, cytarabine, vidarabine, ribavirin, acyclovir, ganciclovir, azidothimidine
Drugs that act on polyadenylation, methylation, capping, and splicing of viral RNA
ribavirin, interferon
Ribavirin inhibits
replication of DNA and RNA viruses including influenza A and B, RSV, hepatitis C, HIV
Ribozymes are
RNA molecules that induce specifically the cleavage of nucleic acids
Nonspecific drug that inhibits protein translation
interferon
What does neuraminidase or sialidase do?
helps spread the influenza virus from cell to cell by removing sialic acid from the surface of infected cells so that viral particles may escape
zanamivir is a potent inhibitor of
viral neuraminidase of type A and B influenza viruses
