Antivirals

Question 1

What do Amantadine and Rimantadine target, and what does this result in?

Answer 1

They target the Influenza A transmembrane protein M2. This is a protein pump which acidifies the interior virion and is necessary for viral penetration.

Question 2

What two viruses is acyclovir most effective against? Which third virus does it have a limited effect on? Why?

Answer 2

Effective against HSV 1 and HSV 2.
Moderately effective against VZV (chickenpox).
The virus thymidine kinase have a higher affinity to acyclovir than the human analogs.

Question 3

What is viral sensitivity to acyclovir dependant upon?

Answer 3

How efficiently the viral kinases phosphorylate the drug.

Question 4

Which antivirals are only effective against Influenza A?

Answer 4

Amantadine and Rimantadine

Question 5

What is valacyclovir? What advantage does it have over acyclovir?

Answer 5

Valacyclovir is a pro-drug of acyclovir. It has much better absorption into the host from the gut.

Question 6

Penciclovir

Answer 6

• Active against HSV1, HSV2, and VZV.
• Similar mechanism as acyclovir.
• Very poor oral absorption so used topically.

Question 7

Oseltamivir and Zanamivir

Answer 7

• Used as pre and post prophylaxis for influenza infection.

- Prevent viral release from infected host cells.

Question 8

Famciclovir

Answer 8

• Pro-drug of penciclovir.

- Well absorbed orally making it a viable method for administration.

Question 9

How long does it typically take for an antiviral to eliminate a herpes infection?

Answer 9

An antiviral will not eliminate herpes. It remains latent in the host.

Question 10

Valganciclovir

Answer 10

• Pro-drug of ganciclovir which can be given, and is well absorbed, orally.

Question 11

What is the general mechanism of the “ciclovir” drugs?

Answer 11

• Block DNA chain elongation (genome replication).
• Compete with the real deoxynucleotides for incorporation into the elongating DNA chain.
• Once incorporated they act as a “dead end”.
• Function against herpesviruses.

Question 12

What is the benefit of the “ciclovir” pro-drugs?

Answer 12

They increase oral absorption allowing for oral administration of the drugs.

Question 13

What are the 4 main sites of actions for antivirals?

Answer 13

1. Blocking viral uncoating in host cells.
2. Blocking viral genome replication.
3. Blocking viral protein synthesis.
4. Blocking release of virus from host cells.

Question 14

What virus do Oseltamivir and Zanamivir act against?

Answer 14

Influenza A and B.

Question 15

Ribavrin

Answer 15

• Nucleoside analogue.
• Interferes with nucleic acid synthesis while inhibiting some viral RNA and DNA polymerases.
• Toxicity to human cells limits human use.
• Used in the treatment of Hepatitis C.

Question 16

Which group of interferons is most clinically relevant.

Answer 16

IFN - alpha

Question 17

How do interferons act?

Answer 17

• Induce productions of proteins creating an “antiviral” state.
• Inhibit viral protein synthesis.
• May decrease stability of viral RNA.

Question 18

What is neuraminidase responsible for?

Answer 18

Neuraminidase is a viral surface antigen responsible for cleaving the bond between emerging virus and infected cell. It helps to release the virus from host cells.

Question 19

Ganciclovir

Answer 19

• Modified version of acyclovir which is effective against CMV (cytomegalovirus) HHV-5.
• Loss of effectiveness against HSV-1, HSV-2, and VZV.