Antivirals Flashcards
HIV entry inhibitors: example and mechanism
Maraviroc
Binds CCR5 on cell, so HIV virus cannot enter cell
HIV fusion inhibitor: example and mechanism
Efuviritide binds viral gp41 (viral surface protein that normally facilitates viral fusion to host cell)
HIV Fusion inhibitor mechanism of resistance
Env encodes structural genes; mutations in env –> resistance
HIV integrase inhibitors: example and mechanism
“-tegravir” (raltegravir, dolutegravir, elvitegravir)
Blocks viral integrase, which normally allows viral DNA (post reverse transcription) to integrate with host DNA
HIV Integrase inhibitors mechanism of resistance
Integrase encoded by pol; mutation here–>resistance
Mechanism of HIV infection–>release
- Attachment (viral gp120 to cell CXCR4 or CCR5)
- Fusion (via viral gp41)
- Uncoating
- Reverse transcription
- Integration into host DNA via integrase
- Transcription, translation
- Protease (bc HIV proteins translated as long polyproteins that need to be cleaved by proteases from immature precursors–>mature virion
NRTIs: what are they?
Nucleoside reverse transcription inhibitors
Indirectly inhibit reverse transcription
Nucleotides or nucleosides with absent hydroxyl @ 3’ end–>DNA elongation terminated because can’t make 3’-5’ phosphodiester bond
NRTIs: how do they get activated in cells?
Nucleosides need to be phosphorylated by cell enzymes to be activated
Nucleotides (ie tenofovir) do not (“naht for tenofovir”)
NRTIs: important SEs overall
Mitochondrial toxicity, lactic acidosis
Lamivudine, stavudine, didanosine SE
peripheral neuropathy
NNRTIs: what are they and how do they work?
Non-nucleoside reverse transcriptase inhibitors
Directly inhibit reverse transcriptase by direct binding–>allosteric inhibition
Doesn’t need intracell phosphor
NNRTIs mechanism of resistance
Mutation in viral pol gene
NNRTIs important side effects
Liver failure
Stevens Johnson Syndrome
Teratogenic (elfavirenz and dilavirdine)
Protease inhibitors: suffix and mechanism
“-navir”
HIV needs proteases bc gene translated as long polyprotein that must be cleaved
Protease encoded by pol gene
Protease resistance?
Mutations of pol gene; never use as monotherapy bc of this
Protease SEs
Hyperglycemia due to insulin resistance, dyslipidemia, lipodystrophy
Ritonovir inhibits CYP450 strongly
Interferons: what are they
Immunomodulatory cytokines released from virus infected cells; upregulated by interleukins
Interferon alpha treats
Hep B and C, hairy cell leukemia, malignant melanoma, kaposi sarcoma, HPV condyloma accuminata, renal cell carcinoma
Interferon alpha SEs
Flu like syndrome (can be very severe), retinopathy, confusion, myelosuppression, drug-induced lupus
Interferon beta tx
multiple sclerosis
Interferon gamma tx
Chronic granulomatous disease
Via activating macrophages
Ribavarin mechanism
Guanosine nucleoside analogue; must be phosphorylated 3x into its active nucleotide form
Ribavirin use
Hep C (not anymore)
Sofosbuvir mechanism
Nucleoside analog, direct polymerase inhibitor
Simeprevir mechanism
Protease inhibitor
HSV, VZV drugs
Acyclovir, valacyclovir, famcyclovir
Acyclovir mechanism
Guanosine nucleoside analog; must be activated by viral thymidine kinase (HSV virus specific)
Absence of viral thymidine kinase confers resistance
Acyclovir gets incorporated into replicating viral DNA, halting synthesis
HSV antivirals that do not need to be activated by virus
Foscarnet and cidofovir
Directly inhibit viral DNA polymerase
Acyclovir SE
CNS (delirium, confusion, hallucinations) Interstitial nephritis (prevent with hydration)
CMV antivirals
gancyclovir, valgancyclovir, foscarnet, cidofovir
Ganciclovir main toxicity
Myelosuppression
When do people get CMV infections?
CD4<50
Ganciclovir mechanism
Like acyclovir (guanosine analog, must be phosphor by viral kinase)
Oseltamivir, zanamivir mechanism and tx for
inhibit influenza NA–>decrease release of progeny virus
Tx and prevent influenza A and B (doesn’t work if already widely replicated virus though, since only inhibits release of more progeny)
Ganciclovir mech of resistance
Mutated viral kinase
Foscarnet mechanism of resistance
Mutated DNA polymerase
