Flashcards in MCM 2-34 Antiviral Drugs Deck (24)
four types of antivirals
nucleoside analogs - RNA/DNA analogs
how can antiviral drugs work (3)
target essential virus functions
-release from cell
-targeting host cell defenses (intrinsic immunity) - interferon pathway
-activate immune response
Nucleic Acid synthesis inhibitors
assembly and release
blocks entry, HIV
blocks uncoating step
nucleic acid synthesis inhibitors - nucs, non-nucs, non nuc polymerase inhibitors, non nuc RT inhibitors
protease/neurominidase inhibitors block assembly/release stage
Antivirals are specific. TF?
true - antiviral drugs are specific, will often target only one virus. Very few broad-spectrum antivirals. Why? Every virus unique, adapted to host, evloved separately, has own enzymes. The small molecules that can be intvented can only fit in tho that specific enzyme.
three major issues about antivirals
most antivirals are highly specific
cytotoxic effects - "off target" effects can harm host cells. "On Target" drugs directed at viral enzymes can be decreased by resistance mutations
Duration of Antiviral Effects
-most drugs are reversible (comeptitive inhibitors)
-virus replication can resume when drug cleared (rebound)
-treatment may need to be life long
describe how antivirals can cause resistance.
Antivirals do not CAUSE resistance, they select for it. The resistance mutations exist in the patient before the drug treatment
what factors favor the emergence of resistant virus variants? (4)
-high rate of viral replication
-high mutation rate (RNA>DNA viruses)
-high selective drug pressure (long term or multiple treatments)
-Immunosuppressed host that cannot clear virus-infected cells
describe virologic breakthrough
as drug is working, the WT will die. Lack of competition causes resistant strain to amplifiy (virologic breakthrough)
Once treatment stops, if WT is more fit, it will come back and take over.
how do we counter antiviral resistance?
-alleviate immunosuppression (reduce doses of anti-T cell drugs)
-combine drugs with different targets, mechanisms can synergize. hard for virus to create mutation resistnace in same genome of same cell to resist both drugs of different pathways.
-target host functions - some viruses depend on certain host functions that we can stop/slow with drugs. viruses cannot mutate to avoid this, can be toxic
analog of guanosine
a-cyclic = is missing the ring
this is a nuceloside analog
gets into all cells, only those with Viral thymidine Kinase will be effected
KEY: activated by viral kinase, substrate of viral polymerase, causes chain termination. EXAM Q
who should be treated?
used for CMV
nuc analog of guanosine, 2 hydroxyls
very toxic, interferes with host DNA polymerase (off target effect)
-CANNOT GIVE TO CHILDREN OR PREGNANT WOMEN
organ transplant patients receive this
for CMV, presents viral DNA from getting inside of capsid (assembly inhibitor)
describe the broad spectrum treatments for DNA viruses
fascarnet and cidofovir
toxic, not super effective.
Hep-B and HIV treatments have similar drugs? why?
Hep-B is based on therapy for HIV because it has a life stage that uses reverse transcriptase.
describe Zanamivir and oseltamivir
neuraminidase inhibitor, sialic drug analogs. Block neuraminidase enzyme.
New drugs focused on polymerase
Broad spectrum, has been used to treat many viruses but isnt very effective. Is OTC in south america
Guanasine analog, not acyclic. Used for HCV and RSV
multiple mechanisms - just not very effective.
First Line HCV therapy
Sofosbuvir + Ns5A(non structural inhibitor) or protease inhibitor is current therapy
Today we treat HEP-C with sofosbuvir + inhibitor for 12 weeks. Must be together EXAM Q)
what can cure HCV?
ledipasvir and sofosbuvir - produces an SVR - sustained viral response, no rebound
brand name sovaldi
nuc analog of uridine
causes chain termination
Must be combined with NS5A inhibitors (-asvir)
what is NRTI? example? used for?
NRTI - Nucleoside Reverse Transcriptase Inhibitor
AZT (nucleoside analog) for HIV treatment
how is HIV currently treated?
1. entry inhibitors
2. RT inhibitors
3. integrase inhibitors
4. protease inhibitors
-must be combined
Classes of HIV drugs
target the different stages of HIV, must be used together
NRTI (nucleoside/tide RT inhibitor)
NNRTI (non-nucleoside RT inhibitor) - binds to different site, non competitive
IN - integrase inhibitors
PI - protease inhibitors