MCM 2-34 Antiviral Drugs Flashcards Preview

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Flashcards in MCM 2-34 Antiviral Drugs Deck (24)
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four types of antivirals

nucleoside analogs - RNA/DNA analogs

Protease inhibitors
entry inhibitors


how can antiviral drugs work (3)

target essential virus functions
-genome replication
-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


describe acyclovir

very safe
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



used for?
what type?
who should be treated?

used for CMV

nuc analog of guanosine, 2 hydroxyls

very toxic, interferes with host DNA polymerase (off target effect)

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


describe ribavarin

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


previr ending?



protease inhibitor

RDRP inhibitor

NS5A inhibitor


describe sofosbuvir

brand name sovaldi

nuc analog of uridine
inhibits RDRP
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?

combination therapy
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

Entry Inhibitors
NRTI (nucleoside/tide RT inhibitor)
NNRTI (non-nucleoside RT inhibitor) - binds to different site, non competitive
IN - integrase inhibitors
PI - protease inhibitors



Can kill viruses with virocidal agents (bleach) or heating/freezing. Typical hygenic measures.

-immunomodulartoy drugs like alpha intereferon
Or direct ancting anvirials- attack structure or metabolism

-Nuceloside analogs - RNA/DNA anlogs
-Non-nucs - everythign else
-protease inhibitory
-entry inhibitors

Target virus life cycle or host defenses (interferon) or activate response

Targeting essential virus functions
Enfurviritide - blocks entry, against HIV
Amatadine/rimantadine - blocks uncoating. Not used anymore.

Nuceleic acid synthesis inhibitors (main class of drugs). Against HIV and herpes
Blocks viral RNA and DNA poly

Protease inhibitors and neuraminidase

Arrange the drugs according to the life cycel



RNA and DNA as building blocks. Many pathways are directed towards creating dna and rna

-test questions are concepts and not for particular drugs
-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.

Cytotoxicity is major problem - to get a drug inside of cell, possible that drugs have offtarget effects - offtarget effects are there because molecule does something you don’t want it to do - harm cells/physiology/toxic
-on target effects can be problem - virus can evolved and mutate, only left with side effects

The duration of antiviral effect, may require lifetime treatment. Herpes and HIV for life. Most are competitive inhbibitor, effects reversible, treatment rqeuires extension

Drug stopped may cause immediate viral rebound. Lifelong treatment has been attractive to drug companies

Inhibits RDRP, targets HCV. QD = daily
Placebo green
Low dose blue 1x
High dose red 1x
Purple low dose 2x
Blue high dose 2x

Dose dependant impact oniviral replication. Amount of virus decreased. After treatment, bounced back up. Body couldn’t clear, but drug could inhibit

2x a day best (high>low), followed by 1x day (high>low). All better than placebo

Resistance exists in patient before the drug. Drug does not cause resistance, drug selects for resistance.
Factors that favor emergene of resistant viruses (4)

Immunosuppressed is more likely to express resistant variants.

Viruses cauase resistance, drugs select for resistance.

As drug is effective, WT die. Only resistant virus is left, no competition - amplifies (virologic breakthrough)

Virologic breakthrough - the resistance type takes over

If wt is more fit, wild type can come back one treatment stops.

Don’t memorize

Important slide

-alleviate immunosuppression, allow it to help. In transplant, reduce anti-t cell drugs (cyclos and steroids)

-must sometimes combine drugs, may be able to target higher levels of viral types. Drugs with different mechanisms can synergize, can target 2 different viral enzymes (protease and polymerase) - hard to create mutation resistance in same genome of same cell to resist drug at the same time in both pathways.

-host function that virus depends on. Virus can never mutate the host function. Virus cannot mutate to avoid, but toxicity is possible (host may also need this function)

Wont be tested on drugs/drug names

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