Anti-viral drugs

Question 1

Do current antiviral drugs target replicating or non-replicating viruses?

Answer 1

Replicating only, as antiviral drugs are virustatic.

Question 2

Why is the host’s immunocompetence important in antiviral therapy?

Answer 2

Current drugs are virustatic only and only affect replicating viral forms.

Question 3

What are the possible targets of anti-viral drugs?

Answer 3

Viral attachment, entry, uncoating, nucleic acid synthesis, later protein synthesis, packaging, viral release.

Question 4

Which drug classes prevent viral fusion with host cells?

Answer 4

Enfuvirtide (binds to gp41 preventing CD4 interaction)
Chemokine receptor antagonists (CCR5)
Palivizumab (binds to respiratory syncytial virus (RSV))

Question 5

Which drug classes prevent viral penetration of host cells?

Answer 5

Neuraminidase inhibitors (also prevent release)
Interferon-alpha

Question 6

Which drug classes prevent viral genome uncoating?

Answer 6

Amantadine (blocks ion channel protein M2 in envelope to prevent influx of H+), used for influenza A

Question 7

Which drug classes inhibit nucleic acid mechanisms?

Answer 7

Viral integrase inhibitor
DNA polymerase inhibiters (guanine analogues - acyclovir, and Foscarnet)
Reverse transcriptase inhibitors (NRTIs and NNRTIs)
RNA polymerase inhibitors

Question 8

Which drugs inhibit protein mechanisms?

Answer 8

Protease inhibitors (immature, non-infectious viral proteins released)
NS3/4 protease inhibitors (inhibit cleaving of enzyme precursors)
NS5A protein inhibitors (block virion assembly)

Question 9

What is the mechanism of action of enfuvirtide?

Answer 9

Prevents entry by binding to glycoprotein subunit gp41 and preventing fusion of HIV to CD4 receptor of host cell

Question 10

What virus is enfuvirtide used for?

Answer 10

HIV (prevents CD4 binding via gp41), in combination, when other treatments have failed.

Question 11

What is the mechanism of action of chemokine receptor antagonists (maraviroc)?

Answer 11

Binds to CCR5 (involved in cell migration)
HIV must binds to CCR5 and CD4 to enter CD4 T cells
Blocks CCR5 interaction and fusion.

Question 12

What is the mechanism of action of interferon-alpha?

Answer 12

Inhibits fusion with host cells
Binds to membrane receptors of infected and nearby uninfected cells to produce enzymes that inhibit viral replication
Enhances phagocytosis of viruses and induces apoptosis of infected cells
PEG extends half-life.

Question 13

What is the mechanism of action of palivizumab?

Answer 13

Monoclonal antibody against surface protein of respiratory syncytial virus (RSV). Binds, neutralises and prevents attachment.

Question 14

What is interferon-alpha used for?

Answer 14

Hep B, hep C

Question 15

What is the mechanism of action of zanamivir and oselramivir?

Answer 15

Block neurominidase, which is required for penetration and release.

Question 16

What are the side effects of zanamivir?

Answer 16

Bronchospasm, dyspnoea (inhaled)

Question 17

What is the mechanism of action of amantadine?

Answer 17

Inhibitor of uncoating by blocking M2 channel proteins to prevent H+ influx from endosome.
May inhibit viral assembly.

Question 18

What are common ADRs of amantadine?

Answer 18

Hypotension, discoloration of skin, hallucinations, neuroleptic malignant syndrome (rare), hyperthermia.

Question 19

What is amantadine used for?

Answer 19

Prevention and treatment of influenza A, Parkinson’s disease.

Question 20

What are neuraminidase inhibitors used for?

Answer 20

Treatment and prevention of influenza

Question 21

What is the mechanism of action of viral integrase inhibitors?

Answer 21

Interfere with DNA replication and translation by inhibiting integration of viral DNA into the host genome.
Inhibits HIV proliferation.
Used with at least 2 active anti-retrovirals.

Question 22

What are the two types of DNA polymerase inhibitors?

Answer 22

Guanine analogues (acyclovir)
Foscarnet

Question 23

What is the mechanism of action of acyclovir?

Answer 23

Guanine analogue and derivative
Prodrug, converted to monophosphate, then triphosphate forms.
Binds to DNA polymerase, required for DNA replication (greater effect)

Question 24

What is the mechanism of action of acyclovir?

Answer 24

Guanine analogue and derivative

Directly and competitively binds to DNA polymerase

Question 25

What are the two types of reverse transcriptase inhibitors?

Answer 25

Nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Question 26

What is the mechanism of action of NRTIs?

Answer 26

Activated by conversion to triphosphate forms Competes with endogenous nucleosides during reverse transcription, incorporated into the DNA chain, inactivating the enzyme.

Question 27

Apart from GI disturbances and headaches, what are the ADRs of NRTIs?

Answer 27

Liver, pancreas, nervous system and kidney toxicity.

Question 28

What is the mechanism of action of NNRTIs?

Answer 28

Bind non-competitively to reverse transcriptase, completely inactivating it.

Question 29

What are common ADRs of NNRTIs?

Answer 29

Rash, hepatotoxicity, CNS effects, drug interactions via CYP-450 Rapid resistance; hence, used in combination.

Question 30

Which has more serious ADRs - NRTIs or NNRTIs?

Answer 30

NRTIs, as NNRTIs are more specific in the action and do not compete with nucleoside triphosphate.

Question 31

What is the mechanism of action of protease inhibitors?

Answer 31

Causes viral release of immature and non infectious proteins.

Question 32

Apart from nausea, vomiting and diarrhoea, what are ADRs of protease inhibitors?

Answer 32

Abnormal fat distribution - SC fat redistributed into upper thoracic and cervical areas, accumulating into a lump, peripheral fat wasting, abdominal fat accumulation. Inhibition of all CYP enzymes

Question 33

What is the mechanism of action of NS3/4 protease inhibitors?

Answer 33

Inhibit cleaving of inactive polypeptides into active functional and structural viral enzymes, inhibiting viral replication.

Question 34

What are ADRs of NS3/4 protease inhibitors?

Answer 34

Skin rash, increased risk of anaemia, CYP3A4 enzyme indicers

Question 35

What is the mechanism of action of ribavarin and sofosbuvir?

Answer 35

RNA polymerase inhibitor when in its TP form Increases mutations rates Enhances host-mediated immunity Synergistic with peg-interferon for Hep C.

Question 36

What are ribavirin and sofosbovir used for?

Answer 36

Severe respiratory syncytial virus (RSV) | Hep C, only in combination with interferon.

Question 37

What is the mechanism of action of NS5A protein inhibitors?

Answer 37

Disruption of replication and virion assembly.

Question 38

What are ADRs of NS5A protein inhibitors?

Answer 38

Nasopharyngitis.