Lecture 5: Antivirals

Question 1

Why are antibiotics ineffective against viruses?

Answer 1

Because antibiotics target things that eukaryotic cells do not have
-because they are targeting bacteria. They are going to target cells walls, ribosomes, DNA polymerase. Viral specific structure are not similar enough to bacteria to be targets for antibiotics

Question 2

What do antiviral target?

Answer 2

Virus-specific function or virus specific structure

Question 3

What are limitations of antivirals?

Answer 3

Drugs are ineffective because too many viruses have been produced by the time symptoms appear.
Viruses also become latent
Viruses mutate rapidly-developing resistance
Difficult to target virus specific processes/structures that are different enough from our cells

Question 4

The most selectively toxic antivirals are

Answer 4

Pro-drugs
Inactive until a virally-encoded enzyme activated it
Only active in virally infected cells
acyclovir, ganciclovir, oseltamivir

Question 5

Interferons

Answer 5

They don’t act directly on the virus,
-instead they activate host genes to interfere with viral replication

Question 6

IFN-a
-virus?
-toxic, why?

Answer 6

Only interferon currently in use to treat viral infections
-chronic HBV, HCV
toxic why? Difficult to target viral specific structures and processes that are different from our cells

Question 7

Entry/fusion inhibitors
-what viruses
-what medications

Answer 7

Block entry of the virus into host cells
-HIV and HSV
-Maraviroc (targets CCR5 co-receptor in HIV)
& enfuviritide (blocks protein responsible for fusion) “enfu” = enters/fusion inhibitors = blocking fusion

Question 8

Uncoating inhibitors
-what do they do and what are medications?

Answer 8

Ion channel blockers
-blocks the viral M2 proteins (this is a protein channel that is required for H+ to enter virion to lower pH for uncoating)
-amantidine, rimantidine

Question 9

Polymerase inhibitors, two types

Answer 9

1. Nucleoside/nucleotide = inhibits active site… analogs (tricks into thinking its a NT, so makes non-functional nucleic acid)
2. Non-nucleoside inhibitors (inhibits by binding anywhere outside the active site to stop nucleic acid production)

Question 10

Nucleotide inhibitor
-what type of polymerase does it inhibit?
-what viruses treated?

Answer 10

-inhibits DNA polymerase
-acyclovir - prodrug activated by a viral enzyme (HSV, VZV)

Question 11

Non-nucleoside inhibitors
-what type of polymerase does it inhibit?
-medication

Answer 11

Inhibits viral RNA polymerase
Binds to a region of the viral RNA polymerase outside the active site altering its function
-Foscarnet

Question 12

Nucleotide inhibitor of reverse transcriptase
-virus

Answer 12

Unique to HIV
-HIV = high mutation rate =anti-retroviral therapy (ART)

Question 13

Non- nucleoside RT inhibitors

Answer 13

Does not bind to active site
Binds to and changes the conformation of RT so no longer functional
Prevents synthesis of DNA from RNA templates

Question 14

Integrase inhibitors

Answer 14

Prevent integration of viral DNA into host genome

Question 15

Protease inhibitors

Answer 15

-preventing cleaving of a protein in the virus that would make them infectious.
can exit the host cell it cannot infect the next cell

Question 16

Neuramonidase inhibitors
-treatment for what viruses?

Answer 16

Treat influenza A and B
-neuramonidase cleaves the sialic acid containing cell receptor
-neuraminidase inhibitors prevent this cleavage!!
Therefore, leaves virions attached to outside of the cell susceptible to immune system responses

Question 17

Vaccines

Answer 17

Not strictly drugs
-can be used for the treatment of known exposures to certain viruses
-incubation Period for some viruses may be long enough, that vaccine can prevent symptoms of the infection