Antiviral Drugs Flashcards
Enfuvirtide
Used for HIV
Mimics HR2 and binds to HR1, therefore preventing actual HR1:HR2 binding. Overall result: prevention of hemifusion stalk and fusion pore, which means virus cannot enter cell.
Maraviroc
Used for HIV
Binds to CCR5 chemokine receptor on CD4+ T-cell, thereby preventing HIV from attaching and entering host cell.
ONLY HIV STRAINS THAT USE CCR5 WILL BE AFFECTED. TEST PATIENT TO SEE WHICH STRAIN HE HAS.
Amantadine and Rimantadine
Used for Influenza A
Influenza enters host cell via endocytosis. The endosome is acidified by H+ proton pump, causing hemogluttinin to undergo a conformation change that allows viral and host membrane fusion. Next, protons enter the virus via the pH-gated proton channel called M2, allowing the viral envelope to open and release its genetic material into cytoplasm of host.
Drugs inhibit the M2 pH-gated proton channel, preventing un-coating and release of genetic material.
Acyclovir and Gancyclovir
Used to treat cytomegalovirus, herpes simplex virus 1 and 2, and varicella zoster virus
Must be activated to a triphosphate form before effective
Target: DNA-dependent DNA polymerase
Acts as a competitive inhibitor of dGTP binding to the viral DNA polymerase; the polymerase remains stuck on pppAcyclovir so that it cannot move to the next pppDTP that binds. The result is chain termination and prevention of DNA viral protein production.
NRTIs
Used to treat HIV-1 and -2
Must be activated by host cell kinases to tri-phosphate form
Target: RNA-dependent DNA polymerase; competitive inhibitor
NRTIs are converted to tri-phosphate nucleotides that provide competitive inhibition of viral reverse transcriptase by competing with endogenous nucleosides for incorporation into viral DNA.
Toxicity: NRTIs can inhibit host cell mitochondrial DNA polymerase, leading to depletion of mitochondrial DNA and therefore mitochondrial dysfunction.
Resistance: Mutations at a number of reverse transcriptase codons.
Drug examples: Lamivudine, Tenofovir disoproxil, Zidovudine (AZT), Abacavir and Emtricitabine
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Lamivudine
NRTI
Tenofovir disoproxil
NRTI
Zidovudine (AZT)
NRTI
Abacavir
NRTI
Emtricitabine
NRTI
NNRTIs
Used to treat HIV-1 only
NO phosphorylation required
Target: The HIV-1 RNA-dependent DNA polymerase at a site DISTINCT from where NRTIs bind - a hydrophobic pocket in the p66 subunit; non-competitive inhibitor because does not bind/block active site
Binding to the pocket alters the 3D structure of the enzyme, inhibiting its activity (this is a direct inhibition of the enzyme, unlike the NRTI mechanism, so host cell toxicity is avoided).
ONLY STRAINS THAT CONTAIN THE p66 SUBUNIT WILL BE AFFECTED; hence, only HIV-1 is affected.
Drug Examples: Efavirenz, Nevirapine
Efavirenz
NNRTI
Nevirapine
NNRTI
Raltegravir
Used to treat HIV-1 and -2
Target: Integrase encoded for by virus
Blocks the catalytic activity of the HIV-1 and -2-encoded integrase, thus preventing integration of virus DNA into the host chromosome.
Resistance: Due to unique target, virus can become resistant through primary mutations in the integrase gene
HIV-1 Protease Inhibitors
Used to treat HIV-1
Target: viral aspartyl protease enzyme
Inhibit above-named enzyme that is responsible for proteolytic cleavage of HIV gag and pol precursor polypeptides that include essential structural components, as well as reverse transcriptase, protease, and integrase. These proteins cannot be produced, so the HIV virus cannot morph into its mature infectious form.
Toxicity: Ritonavir inhibits CYP3A4 metabolic capacity, which means that it can be used in low doses with other drugs, thus prolonging their presence in the plasma.
Resistance: It initially occurs in the active site of the enzyme, with secondary mutations arising at distant sites on the enzyme.
Drug Examples: Atazanavir, Ritonavir, and Saquinavir
