AA antivirals

Question 1

What are the stages of viral replication

Answer 1

• Attachment
• Entry/ fusion
• Fusion/uncoating
• Transcription
• Replication of viral nucleic acid
• Translation
• Assembly
• Release

Question 2

Whats the difference between transcription and translation

Answer 2

Transcription
* Creation of complementary RNA copy from DNA
* With the help of reverse transcriptase
o RNA –> DNA

Translation
* Assembly of protein from RNA using ribosomes

Question 3

What is the mechanism of action of aciclovir

Answer 3

Aciclovir has an incomplete sugar backbone - missing 3` OH

1. Phosphorylation of OH group by viral thymidine kinase
   a. Formation of aciclovir monophosphate
2. Cellular kinases adds 2 phosphates to aciclovir monophosphate = activation
3. Aciclovir triphosphate blocks formation of guanosine triphosphate for viral DNA

Question 4

What are some resistance mechanisms against aciclovir?

Answer 4

• Reduced thymidine kinase activity
• Altered thymidine kinase
• Altered DNA polymerase

Question 5

What are some aciclovir analogues

Answer 5

Ganciclovir
* Viral phosphotransferase adds phosphate to ganciclovir –> ganciclovir monophosphate
* Cellular kinase adds 2 phosphate –> ganciclovir triphosphate = activated
* Blocks formation of deoxyguanosine triphosphate

Cidofovir
* Cellular kinases adds 2 phosphate = activated
* Blocks formation of deoxyguanosine triphosphate

Foscarnet - non-nucleoside
* Directly blocks the formation of guanosine triphosphate

Question 6

What are some antivirals for influenza

Answer 6

Neuraminidase
* Blocks release of progeny viral particles from infected cells by stopping cleavage of HA from the sialic acid on cell surface

Matrix protein inhibitors
* Blocks M2 protein channel and stops uncoating

Polymerase inhibitors

Question 7

What are ribavirin

Answer 7

Analogues to guanine and adenine

Against RNA and DNA viruses
RNA –> inhibit RNA polymerase
All viruses
* Inhibits inosine monophosphate dehydrogenase = reduced intracellular GTP
* Inhibits capping of mRNA = stop translation
* Inhibits polyadenylation of mRNA = inhibits translation
* Enhances antiviral immune responses by converting host T cell to type 1 = 1 allergic to anti-infective

Question 8

What are enterovirus capsid protein blockers

Answer 8

Binds to capsid protein and blocks virus attachment

• Pleconaril
• Pocapavir

Question 9

What are the antiviral therapy for heptatis C

Answer 9

Antiviral therapy
o Alpha interferon for 6months
o Ribavirin with alpha interferon (40-55%)
o Ribavirin with pegylated interferon (55%)
o Interferon with direct acting antiviral (75%)
o Combination of direct acting antiviral drugs (90-100%)

Question 10

What are some direct acting antiviral for hepatitis C

Answer 10

• Direct acting antiviral
  o NS3/NS4a protease inhibitor
• Cleave four specific sites on protease
  o NS5B polymerase inhibitor
• Interfere with viral replication
• Binding to NS5B RNA dependent RNA polymerase
  o NS5A inhibitor
• Prevents formation of replication complex and regulation of replication as well as assembly of viral particles

Question 11

What is highly reactive anti-retroviral therapy (HAART)

Answer 11

Nucleoside RT inhibitor
o With nucleoside/nucleotide RT inhibitor OR non-nucleoside RT inhibitor
o Add protease inhibitor

Reduces viral load and improves CD4 count

Question 12

What are interferons

Answer 12

Inhibition of viral replication
* Immune activation by stimulation of NK cells, induction of B cell proliferation and enhancement of MHC class 1 expression on cell surface which increases recognition of virus infected cells by cytotoxic cells