Lecture 2 Flashcards
What are the main three defenses against viruses?
- Host defenses
- Control (vaccines)
- Antiviral drugs
What are the three types of viral vaccines that are available?
- Inactivated (genome destroyed, capsid intact-polio)
- Attenuated (extremely slow release of live virus-pox, MMR)
- Genetically engineered (viral proteins produced in yeast cells)
What are the two main aspects that an antiviral drug can target?
- Specific viral function (like an enzyme needed for viral life cycle)
- A cellular function virus needs in order to replicate
If an antiviral drug targets a cellular function that a virus needs to replicate, what are the two main things that must happen?
- Must not be a crucial function to cell or
2. Only will kill virus-infected cells
In regards to antiviral drugs, what is viral disruption?
- Disrupting enveloped viruses
- (Nonoxynol-detergent for HSV, HIV)
- (Citric acid-common cold rhinovirus)
In regards to antiviral drugs, how can they target viral attachment?
- As antibodies that bind to virus
- Can’t interact with receptors
- Cause viral particle aggregation
In regards to antiviral drugs, what are receptor antagonists?
- Binds to receptors so virus can’t
* Maraviroc is one such agent
In regards to antiviral drugs, what are fusion inhibitors?
- Stop enveloped viruses from getting into cell
* Important to stop HIV from getting into CD4 (enfuvirtide)
- In regards to antiviral drugs, how do drugs that target uncoating work?
- Two examples?
- Stop proton flow which inhibits uncoating
* Amantadine and rimantadine are two examples
What five drugs are nucleoside analogs that inhibit viral polymerase by causing chain termination?
- Acyclovir
- Ganciclovir
- Azidothymidine
- Acyclic nucleoside phosphonates (cidofovir, tenofovir)
- Telbivudine
What three drugs are nucleoside analogs that cause errors in replication and transcription?
- Ribavirin
- Trifluorothymidine
- Idoxuridine
What are non-nucleoside analogs that still target nucleic acid synthesis?
- Foscarnet
2. Nevirapine
What is the general mechanism of action that nucleoside analog drugs use to inhibit nucleic acid synthesis?
- Taken up by cells
- Converted by viral and cellular enzymes to triphosphate form
- Triphosphate form inhibits DNA and RNA polymerase
- Incorporated into growing DNA leading to abnormal proteins and breakage
Acyclovir details?
- Mainly for HSV 1 and 2 treatment
- Purine mimic
- 100x affinity for viral DNA polymerase
- Looks like deoxyguanosine
- ↓ pain and ↑ healing of sores from chickenpox, h. zoster, and genital herpes
- Prevent outbreaks of genital herpes
Ganciclovir details?
- Herpes virus, CMV (however CMV does not encode a thymidine kinase)
- 30x affinity for viral DNA polymerase
- 2-deoxyy-guanosine analogue
- Can cause bone marrow suppression and CNS effects
- Drug of choice for CMV infection: retinitis, pneumonia, colitis