Antiviral Drugs Flashcards
Examples of host defenses?
Mechanical, Chemical, Biological Barriers.
Immune System
Non-intrinsic ways viruses can be controlled?
Vaccines, anti-viral drugs
Three kinds of vaccines?
Inactivated, Attenuated, Genetically Engineered
What are inactivated vaccines?
Genome of virus destroyed, caspid intact (polio)
What are attenuated vaccines?
Live viruses that are extremely slow are replication (MMR)
What are genetically engineered vaccines?
viral proteins are produced by yeast cells, concentrated, and purified (hep B)
Why do we need antiviral agents?
Many diseases don’t have vaccines
Fast mutation
Reassortment
Immunosuppresive Diesease
barriers to effective antivirals?
Only targeting the virus
Resistance from mutation
Late symptoms
Intracellular
Name some viruses that have anti-viral drugs.
Herpes simplex varicella Zoster cytomegalovirus HIV Influenza Hepatitis
Viral disruption can be utilized against…
Give two examples
Enveloped Viruses
N9 - detergent HSV and HIV
Citric Acid - Common Cold/Rhinoviruses
How might an anti-viral inhibit viral attachment?
Antibodies bind to a virus – aggregation or interference with receptor binding
Receptor antagonist – ex. change CCR receptor to stop HIV binding
Fusion inhibitors – (ex. enfuvirtide) inhibit the ability of HIV to get into T cells
Name two antivirals for uncoating.
Amantadine
Rimantadine
How do adamantanes work?
They target M2 protein to block a H+ pump required in the process of viral uncoating.
What do you treat with amantadine?
Influenza A
What are two ways to target nucleic acid synthesis?
Nucleoside analogs and non-nucleoside analogs
What are two ways that nucleoside analogs can work?
Inhibition of viral polymerase via chain terminations
Errors in replication/transcription
What is acyclovir used to treat?
Herpes infections
How does acyclovir work?
Acts as a purine mimic, but lacks the 3’ hydroxyl.
Converted by HSV thymidine kinase (viral) so only infected cells will be exposed.
Acyclovir triphosphate incorporates into the DNA chain and has no 3’ OH, so termination is cancelled.
How does Ganciclovir work?
A synthetic analogue of 2-deoxyguanosine – similar to acyclovir using a different kinase)
What is Ganciclovir used to treat?
All herpes viruses – including cytomegalovirus
What is azidothymidine?
An analog of thymidine with the 3’OH replaced with an azido group.
How does azidothymidine work?
Inhibits reverse transcriptase function, causing premature DNA chain termination.
What is azidothymidine used to treat?
HIV
What are acyclic nucleoside phosphonates? Give two examples.
Nucleoside analogues with a P attached to a sugar. No need for phosphorylation
Cidofovir and Tenofovir
What are cidofovir and tenofovir used to treat?
Cidofovir – CMV, Retinitis in AIDS
Tenofovir – HBV and HIV
What is telbivudine? What does it treat?
A synthetic thymidine nucleoside analog that inhibits viral DNA polymerase.
HBV
What is ribavirin? How does it work?
Ribavirin is an analog of the nucleoside guanosine, but with an open ring structure. It is incorporated into RNA, and because of its compatability with U and C, it introduces mutations.
Used to treat a lot of different viruses.
What is triflourothymidine?
A thymidine analog with a CF3 group added the the uracil part to block base pairing. It is Pd by cellular enzymes.
What is triflourothymidine used to treat?
epithelial keratitis caused by herpes virus
What is idoxuridine? What do you use it to treat?
Idoxuridine substitutes for thymidine in viral DNA. Same as acyclovir, except host cells can also P, so it is less selective.
Herpes Simplex Virus
What is foscarnet? How does it work?
Simple compounds resembling pyrophosphate
Bind to pyrophosphate-binding site of DNA pol to block nucleotide binding
What do you treat with foscarnet?
Herpes, HIV, CMV
What are nevirapine, efavirenz, and delavirdine?
Non-nucleoside transcriptase inhibitors
They bind directly to RT and block the enzyme’s catalytic site.
Doesn’t require P.
What are nevirapine, efavirenz, and delavirdine used to treat?
HIV
What do integrase inhibitors do?
Inhibit the integration of DNA into the genome.
What is interferon?
Glycoproteins that interfere with replication of the virus by inhibiting protein synthesis of the infected cell
Types of Interferon?
IFN-alpha –> virus infected APCs
IFN-beta –> virus infected fibroblasts
IFN-gamma –> activated T cells
What induces interferon activity?
dsRNA, interactions with sense/anti RNA with DNA viruses, or envelop interaction with DCs
Mechanism of interferon activity?
Initial infected cell releases IFN
Binds to specific receptor and induces antiviral state by synthesis of PKR, 2-5 oligoadenylate synthetase
Results of interferon activity
mRNA is degraded and protein synthesis is inhibited to block viral replication (by 2-5 oligoadenylate synthetase)
Inhibition of ribosome assembly (PKR) by inhibiting elf-2alpha
What does interferon do to help the initially infected cell?
Nothing.
Name some protease inhibitors.
Saquinavir, Indinavir, Nelfinavir, Ritonavir
What are protease inhibitors? What do they treat?
They prevent viral replication by inhibiting the protease use the cleave polyproteins into their final rpoducts.
Treats HIV and Hep C
How do neuraminidase inhibitors work? Name two.
They catalyze the clevage os sialic acid residues on glycoproteins/lipids, making virons unable to detach and leave the cell.
What are neuraminidase inhibitors used to treat?
Influenza A and B
