S9) Antiviral Agents

Question 1

Identify and describe four agents which directly inactivate viruses (virucides)

Answer 1

• Non-organic (detergents, chlorine-based agents)
• Organic solvents e.g. ether, alcohol, chloroform
• Radiation e.g. UV light, laser therapy for warts
• Cryotherapy e.g. for warts removes lesions but may not inactivate virus itself

Question 2

What is the limitation of virucides?

Answer 2

These agents cannot be used systemically, and only in specific situations topically

Question 3

What are the six steps in viral replication?

Answer 3

⇒ Attachment

⇒ Uncoating

⇒ RNA/DNA replication

⇒ Protein synthesis

⇒ Assembly

⇒ Release

Question 4

Identify some agents which inhibit viral replication

Answer 4

Question 5

What are the limitations of agents that inhibit viral replication?

Answer 5

• Interference with host-cell metabolism can result in adverse effects
• Ineffective against non-replicating/latent viral infections
• May exhibit rebound effects when drug is stopped
• Possible development of drug resistance

Question 6

What do immunomodulators of host response to viral infection do?

Answer 6

• Replace deficient host immunity e.g. immunoglobulins for HBV, VZV
• Enhance host immunity e.g. interferons, Imiquimod

Question 7

What are immunoglobulins?

Answer 7

Immunoglobulins are pooled human sera from blood donors, containing preformed antibodies (IM/ SC/ IV injection)

Question 8

Identify five immunoglobulins and the conditions they are used to treat

Answer 8

• HBIG – HBV
• VZIG – VZV
• HRIG – Rabies
• VIG – Vaccinia
• HNIG – HAV, measles, polio rubella

Question 9

What are the different groups of anti-herpes drugs?

Answer 9

• Aciclovir
• Ganciclovir
• Cidofovir
• Foscarnet

Question 10

Aciclovir is an anti-herpes virus drug.

How does antiviral resistance arise?

Answer 10

Resistance arises via absent/ reduced TK enzyme, or altered TK substrate target, or altered DNA polymerase

Question 11

What are some adverse drug reactions of aciclovir?

Answer 11

• Lethargy
• Confusion
• Tremor
• Hallucinations
• Myoclonus

Question 12

In four steps, explain how aciclovir acts to inhibit viral DNA polymerase

Answer 12

⇒ Aciclovir molecules enter the cell

⇒ HSV enzyme TK converts it to aciclovir monophosphate

⇒ Human enzymes add 2 more phosphates to form the active drug acyclovir triphosphate

⇒ Aciclovir triphosphate competes with dGTP as a substrate for viral DNA polymerase + acts as a chain terminator

Question 13

What are the different groups of anti-hepatitis drugs?

Answer 13

• Lamivudine
• Adefovir
• Emtricitabine
• Entecavir
• Ribavirin

Question 14

How do lamivudine and adefovir act?

Answer 14

Both act as false substrate and chain terminator of reverse transcriptase (RT) enzyme in HIV and HBV replication

Question 15

What are interferons?

Answer 15

• Interferons are naturally produced substances by the body’s non-specific innate immune system
• They are potent cytokines – immunomodulating, antiproliferative

Question 16

Which viruses are interferons used to treat?

Answer 16

• HBV
• HCV

Question 17

Oseltamivir is an anti-influenza drug.

What is its mechanism of action?

Answer 17

Reversible inhibitors of viral neuraminidase enzyme that cleaves sialic-acid receptor-HA bond between host cell and virus

Question 18

How does antiviral resistance to osetamivir arise?

Answer 18

Resistance arises due to mutations in NA gene (H274Y/ H275Y), producing a less fit virus.

Question 19

Oseltamivir is generally well tolerated.

Regardless, what are some of its adverse effects?

Answer 19

• Nausea
• Vomiting
• Abdominal discomfort
• Rashes
• Headaches

Question 20

Identify five different groups of anti retroviral (HIV) drugs

Answer 20

• Nucleoside reverse transcriptase inhibitors (NRTIs)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Protease inhibitors (PIs)
• Fusion inhibitors (FIs)
• Integrase inhibitors (INIs)

Question 21

Provide three examples of NRTIs

Answer 21

• Zidovudine (AZT)
• Didanosine (ddI)
• Lamivudine

Question 22

Describe the mechanism of action of NRTIs

Answer 22

- NRTIs act as false substrates and lack the 3’-OH group for DNA elongation, so when incorporated, will terminate production of the HIV DNA provirus

• Also, Inhibit the DNA polymerase function of the HIV RT enzyme

Question 23

Identify some ADRs of NRTIs

Answer 23

• Lactic acidosis
• Hepatomegaly
• Steatosis
• Hyperlactaemia

Question 24

Describe the mechanism of action for NNRTIs

Answer 24

NNRTIs are non-competitive inhibitors of HIV RT by allosteric inhibition of enzyme function, binding at different sites from the NRTI sites

Question 25

Identify some ADRs of NNRTIs

Answer 25

- Erythematous maculopapular rash - Raised LFTs - CNS symptoms