micro lecture 15 Flashcards
how do Viruses pose a new set of problems for antivirals?
They are obligate intracellular parasites
Because they “hijack” many host cellular processes, selective toxicity is more difficult
Many viruses difficult to culture - more difficult to test potential antiviral drugs
The lack of easy, rapid tests means it is difficult to differentiate between various viral infections
Many viruses have multiple strains and also will readily mutate
list facts about aciclovir as an antiviral drug
Virus-specific and “relatively” nontoxic
Effective against both genital, oral and more serious herpes simplex (HSV) infections
Also used with some success in treatment of varicella virus (chickenpox and shingles)
It can be given intravenously or orally or used topically
what is the mechanism of action for aciclovir?
Nucleoside analogue produced as a prodrug (acycloguanosine)
-Phosphorylated once in the patient’s cells
IF virally coded thymidine kinase is present
-Affects DNA polymerases encoded by viral genes, so
effective “only” in infected cells:
Blockade and termination of viral DNA replication
what are the new variations of aciclovir?
valaciclovir, famciclovir, penciclovir
list facts about ganciclovir
Derivative of aciclovir
Developed to treat cytomegalovirus (CMV) infections
A well-absorbed oral prodrug has been produced (valganciclovir)
Used effectively for cytomegalovirus in immunocompromised patients
More toxic, particularly to bone marrow
(classified teratogen, mutagen, carcinogen)
list facts about foscarnet
foscarnet acts against DNA replication by inhibiting pyrophosphate binding to DNA polymerases
(greater affinity for virally coded versions but only RELATIVE specificity)
It is generally used to treat herpes/CMV
infections when aciclovir/ganciclovir unsuitable
Toxic to kidneys, principally (approx 40% pts)
list facts about oseltamivir and zanamivir
Selective inhibitor of viral neuraminidase (NA)
Glycoproteins on the virion surface, important for entry into cells and for the release of recently formed virus particles from cells, allowing spread within the body.
Used to prevent infection after exposure, or treat
In uncomplicated influenza, slightly shorter duration of symptoms but may be significant in patients at risk of severe complications
(must start within 36-48hrs of symptom onset or exposure to infected person)
list five types of HIV antiretrovirals.
Entry/fusion inhibitors
Nucleoside Reverse Transcriptase Inhibitors (RTIs)
Integrase Inhibitors (INIs)
Protease inhibitors (PIs)
which HIV antiretrovirals represents this statement “rarely used, resistance too common”
Entry/fusion inhibitors
describe Nucleoside Reverse Transcriptase Inhibitors (RTIs)
(nucleoside, nucleotide or neither)
This is a viral enzyme, so useful target. HIV nucleic acid is RNA, so must be “translated” into DNA. In slightly different ways, these drugs all inhibit the process
The “base mimics” are included in the DNA chain but can’t be added to (no 3’OH), so formation is stopped
Non-base inhibitors bind directly to the enzyme
describe Integrase Inhibitors (INIs)
Integrase is a viral enzyme that “integrates” the newly transcripted DNA into host DNA.
The current drugs interact with two Mg2+ ions in the enzyme’s active site structure
describe Protease inhibitors (PIs)
Protease is a viral enzyme that is involved in building new virus particles from the various parts that the host cell has manufactured. These drugs tend not to stop the assembly but the resulting virus particles (virions) are defective
