Antiviral Drugs Flashcards by Chris Rodarte

Antivirals are generally

virostatic

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Cross resistance example given with TK mutation

Idoxuridine and acyclovir

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Three categories of agents that prevent entry

Attachment inhibitors

Coreceptor antagonists

Fusion inhibitors

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Maraviroc MOA

CCR5 coreceptor antagonist

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HIV1 can resist maraviroc by

using drug-bound form of CCR5

This is called nonompetitive resistance

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Cenicriviroc MOA

dual CCR5 and CCR2 antagonist

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Enfuvirtide MOA

inhibits gp41

(derived from natural gp41 HR2 sequence)

**does NOT have good oral BA

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Inhibition of uncoating at the level of the endosomme/lysosome may be a good target because it…

takes place at a specific pH (low)

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Arildone MOA

inhibits picornavirus uncoating

*inserts into a canyon in the VP1 viral protein and blocks ion transport

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Plecoranil MOA

stops shedding of nucleocapsid proteins from RNA

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First integrase inhibitor

Raltegravir

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Second generation integrase strand transfer inhibitor (INSTI)

Dolutegravir

has a limited cross-resistance profile

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Best class of AV drugs

Ones that act on replication of the genome

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Because thymidine kinase is _____, nucleoside analogs can be administered in _______ form.

This provides what sort of advantage?

Viral TK is less specific

administered in unphosphorylated form

*Un-P drug enters cells more easily than phosphorylated ones

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Nucleoside analog drugs generally cause ____

chain termination

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Examples of nucleoside analogs

Idoxuridine

Ribavirin

Acyclovir/Gancyclovir

Azidothimidine

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Two drugs that can interfere with mRNA transcription processing

Ribavirin

Interferon

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Drugs that target proein translation

no specific inhibitors!

Interferon is non-specific for this

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Post-trans modifications that can be targetss

glycosylation

phosphorylation

myristoylation

sialidation

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Neuraminidase inhibitor drugs

Zanamavir

Oseltamavir

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Neuraminidase function

“sialidase” = removes sialic acid from surface at level of glyccoproteins and glycolipids

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Zanamavir MOA

inhibits NA of influenza A + B

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Zanamavir requires

aersosol delivery

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Oseltamavir is an analog of

carbocyclic sialic acid

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Other drug related to NA inhibitors

laninamivir

What is nirazoxamide?

a thiazolide it might block **glycosylation of viral hemagglutinin** in the Golgi

Nitazoxanide is effective against

Yes

Protease inhibitors are all \_\_\_\_ Examples?

substrate analogs Aquinavir, ritonavir, indinavir, lopinavir, tipranavir, darunavir

Protease inhibitors for HCV

Boceprevir and Telprevir

Amantadine is \_\_\_

lysosomotropic

Amantadine MOA

Inhibits viral RNA uncoating (A only) also acts on maturation of influenza hemagglutinin glycoprotein = reduce infective potential

Rimantadine vs amantadine

3-4x greater activity less toxic

Idoxuridine MOA Uses? Alternative drug?

Pyrimidine analog that inhibits viral DNA synthesis after activation by phosphorylation by TK mainly for Herpes and Poxviruses, but has HIGH TOXICITY so isnt really used Trifluridine = used topically for **herpes keratitis + primary keratoconjunctivitis**

Nuceoside analogs of cytosine and adenine They require...

Cytarabine + Vidarabine both have to be phosphorylated to be active

Ribivirin is a \_\_\_. Inhibits \_\_\_\_\_\_\_\_

triazole inhibits 5' cap formation on mRNA

Ribavirin toxicity

dose-dependent HA mutagen and teratogen

Acyclovir MOA

Purine analog that competes with dGTP Two pronged effect: 1. Binds to and inhibits Viral Polymerase 2. Terminates the chain (doesn't have a 3' OH)

Acyclovir causes tissue irritation if \_\_\_\_\_

extravasation occurs when given IV

Acyclovir uses

Herpesviruses | (HSV, VZV, EBV, CMV)

What is valacyclovir? Other related drugs?

Prodrug to acyclovir (3-5x higher levels) Famciclovir \>\> penciclovir

Gancyclovir MOA

Similar to acyclovir, but initial phosphorylation can be carried out by cellular enzymes \*\*selectivity is due to the fact that it is 30x higher affinity for viral enzymes

Gancyclovir major toxicity (tissue) and use?

Toxicity = rapidly dividing tissues Use for AIDS-related CMV infections

AZT MOA

Chain terminator that is phosphorylated by cellular enzymes ( = can be used against viruses that dont bring own kinase) Reverse transcriptase is **more sensitive to AZT** than host DNA pol, therefore it is targeted to infected cells

Mutants against AZT tend to have...

changes in RT

AZT AE's are mainly \_\_\_\_\_

hematologic | (granulocytopenia and anemia)

AZT commonly used with ____ for \_\_\_\_\_

Lamivudine (cytosine analog) HIV

In addition to AZT, HIV treatment may involve _______ and \_\_\_\_\_\_

**Dolutegravir** (INSTI) NRTI's **Abacavir** and **Lamivudine**

Lamivudine is very efficient againt

HBV

Adefovir MOA and use Toxicity?

Analog of **adenosine monophosphate**... competitively inhibits HBV DNA polymerase Dose dependent nephrotoxicity

NNRTI MOA and recommended use

noncompetitive inhibitors that physically prevent RT from working should NOT be used as monotherapy (d/t resistance)

5 NNRTIs

N/D/E Etravirine, Rilpivirine

Drug that prevents HIV transmission to neonate

Neviripine

Drug used in HIV patients in combo with at least two active drugs

Etravirine

Competitive inhibitor of DNA polymerase that binds to **pyrophosphate** site

Foscarnet also an inhibitor of RNA pol and HIV RT Particularly potent to inhibit herpes DNApol

Foscarnet effective for \_\_\_\_

CMV retinitis

Protease inhibitors generally prevent \_\_\_\_

the maturation of viral particles

Protease inhibitors have been developed against...

the active site of **aspartyl protease** of HIV *This protein is NOT similar to any known host proteolytic enzyme*

Saquinavir is the \_\_\_\_

least effective PI

PI that has ben shown to reduce death by 58%

Ritonavir Used in combo therapy with other PI's

Amprenavir or fosamprenavir are generally used as \_\_\_\_

combo therapy

PI that has lower level of resistace

**Darunavir** Approved for treatment-naive patients

Given with ritonavir for salvage option

Tipranavir

Benefit of Indinavir

Reduces HIV load (PCR can't even detect in 85% of patients)

Protease inhibitors for HCV What do they target?

Telaprevir and boceprevir target NS3.4A HCV serine protease

Target of Asunaprevir

NS5A inhibitor

Drug that targets the viral terminase complex

Letermovir

alpha and beta interferon mechanisms

1. bind to specific receptors on adjacent cells and protect from viral infection 2. enhance MHCI and MHCII on infected cells = enhance viral antigen presentation

What is truvada

emtricitabine/tenofovir disoproxil fumurate Used fo preexposure prophylaxis

Adamantanes mechanism

M2 ion channel inhibitors

Gamma interferon secreted by \_\_\_ Function?

T cells Enhances specific Tcell mediated immune response

general interferon functions (2)

Enhance specific immune response Have direct antiviral effects (penetration, uncoating, degradation, inhibition of mRNA synthesis or methylation)

How do interferons interfere with protein synthesis?

Phosphorylating EIF-2

Single point mutation at different positions of M2 is sufficient to...

induce cross-resistance to amantadine and rimantadine

Oseltamavir vs Zanamavir - ages

Oselt = 1 yr. Zan = 7 for treatment, 5 for chemoprophylaxis

Sensitivity for RIDT's (rapid influenza diagnostic tests)

10-70%

Treatment vs lab confirmation of influenza

Treatment should NOT wait for lab confirmation of influenza