Antiviral Agents

Question 1

What are the three outcomes of host cells that are virally infected?

Answer 1

1. Host cell is lysed (typically RNA virus-mediated i.e. influenza
2. Host cell is persistently infected = low levels of dz can be detected chronically and can recur
3. Host cell is latently infected = dz is undetectable and may recur. *These types of infections are not treatable with current antivirals

Question 2

What are our primary means of viral control?

Answer 2

Public health measures

prophylactic vaccines

Question 3

What are the 5 main stages of viral life cycle steps?

Answer 3

1. Viral attachment/entry/penetration
2. Uncoating (intracellular)
3. Protein synthesis and processing of virus (intracellular)
4. Packaging and assembly of virus (intracellular)
5. Viral release (intra/extracellular)

Question 4

What is an endosome?

Answer 4

Viral hemagglutinin envelope + cell plasma membrane envelope

Viral envelope surrounded w/ hemagglutinin (extracellular) which is then endocytosed into cell and surrounded w/ cell plasma membrane

Question 5

What do viral neuraminidases (NA) do?

What do NA inhibitors do?

Answer 5

Basically allow packaged virus at cell surface to be cleaved (i.e. released into extracellular environment)

Prevent the cleavage of viral packages at cell membrane. Also prevents entry of virus through mucin secretions of respiratory cells which reduces infection

Question 6

What are some NA antivirals and how are they administered?

Answer 6

oseltamivir (Tamiflu) PO X 5d
zanamivir (Relenza) Inhalation BID X 5d
peramivir (Rapivab) IV single dose

Question 7

What is a polymerase acidic (PA) endonuclease? Which antiviral drug is in this class?

Answer 7

Critical in translation of viral mRNA via “cap-snatching” mechanism. PA antivirals inhibit cap-dependent endonucleases

Xofluza (baloxavir) currently only one but,
favipiravir is under development

Question 8

when do influenza antivirals need to be started?

Answer 8

Within first 48 hrs of symptom onset by either A or B

This decreases severity and duration by 1-2 days (80-90% effective)

Question 9

How does a virus uncoat? What drugs are in this class?

Answer 9

Influenza A ONLY has virally encoded H+ ion channel (M2 protein) and this channel is what is blocked by antiviral drugs;

1. amantadine
2. rimantadine

*In 2014 most influenza A strains were resistant which is why we do not see this used much today

Question 10

How is amantadine administered? Where does it accumulate and how is it excreted?

Answer 10

PO with accumulation in lungs
Kidneys as 90% unchanged drug
*Requires dosage adjustment for renal impairment

Question 11

How is rimantadine excreted? Contraindications?

Answer 11

Hepatically eliminated

• half-life of 12 hrs i.e. 1-2 tabs daily
• Excreted in breast milk, contraindicated if breast feeding causes urinary retention, emesis, skin rash

Question 12

How do viral DNA polymerase inhibitor drugs work?

Answer 12

1. They have 200X affinity for viral thymidine kinases (this is “on-switch” for replication)
2. Cellular (host cell) kinases convert acyclovir-MP (inactive) to acyclovir-TP making it active again
3. Acyclovir-TP also binds with greater affinity to viral DNA polymerase and is incorporated into viral DNA strands
4. These acyclovir incorporated strands stop DNA replication therefore strand elongation and these strands irreversibly bind VIRAL DNA polymerase inactivating them (suicide inactivation)

Question 13

What are the names of some viral DNA polymerase inhibitors?

Answer 13

acyclovir
valacyclovir
penciclovir
famciclovir

Question 14

What are viral DNA polymerase inhibitor drugs used against?

Answer 14

HSV
HSV encephalitis
HSV keratoconjunctivitis (topical vidarabine and trifluridine)
Varicella Zoster Virus

Question 15

Inhibitors of viral penetration drug name?

Answer 15

Docosanol

• topical
• needs to be applied in prodrome phase
• not therapeutic if applied during papular or later stages