Antivirals

Question 1

Broad spectrum antivirals aim?

Answer 1

work by ↓ viral genome replication

Question 2

What are some properties of Broad spectrum antivirals?

Answer 2

• generally lower potency
• quickly become resistant to monotherapy
• used for emerging viral pathogens
• used for some viruses for which there are not extensive DAAs available for

Question 3

what are DAAs?

Answer 3

specifically target a specific viral protein/process

higher activity

Question 4

What are the 4 main DAA targets?

Answer 4

1. Nucleoside/nucleotide analogues
2. Viral protease inhibitors (HIV, SARS-CoV-2, HepC)
3. Non-nucleotide inhibitors
4. Integrase inhibitors (HIV, HepB)

Question 5

Acyclovir (NRTI) therapeutic effect and moa?

Answer 5

therapeutic effect: early RNA/DNA chain termination

first phosphorylated by cellular kinase

inhibits viral DNA polymerase ie reverse transcriptase

Incorporation of acyclovir triphosphate into DNA results in chain termination

Question 6

efavirenz (NNRTI) therapeutic effect and moa in HIV

Answer 6

therapeutic effect: inhibit RT

efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase)

phosphorylated to triphosphate form (active)

less virions copied

Question 7

Ritonavir moa (viral protease inhibitor)?

Answer 7

normal virus:
produces viral protease → cleaves polypeptide to functional subunits to produce virions

ritonavir:
inhibits HIV protease, but also inhibits CYP450 activity

used in combination with other protease inhibitors to increase their bioavailability

Question 8

integrase inhibitor (raltegravir) moa?

Answer 8

raltegravir inhibits the activity of HIV-1 integrase

blocks insertion of HIV-1 DNA into the host cell genome

used for complex HIV where other DAAs resistance has occurred

Answer 9

• nucleoside cant be used as monotherapy as it takes 1-2 mutations in HIV genome for it to become ineffective
• compared to protease inhibitors which takes 4 mutations for it to become ineffective
• when combined we can increase the BtR

Question 10

What is barrier to resistance?

Answer 10

The genetic barrier to resistance refers to the number of mutations in an ARV’s therapeutic target that are needed to confer a clinically meaningful loss of susceptibility to the drug.

Question 11

Why cant we use nucleoside inhibitors as monotherapy?

Answer 11

• nucleoside cant be used as monotherapy as it takes 1-2 mutations in HIV genome for it to become ineffective
• compared to protease inhibitors which takes 4 mutations for it to become ineffective
• when combined we can increase the BtR

Question 12

What is SVR (sustained virologic response)?

Answer 12

Sustained virologic response means that the hepatitis C virus is not detected in the blood 12 weeks or more after completing treatment.

Question 13

SVR Stages?

Answer 13

1. baseline: initlaly many copies and enters treatment period
2. treatment period: involves a nucleotide analogue alongside protease inhibitor, treated for 12 weeks
3. follow up: 12 week follow up, bloods taken to check HCV RNA copy number. if this below that figure then we have sustained virologic response

Question 14

why do we need immunotherapy?

Answer 14

viruses induce pro-inflam immune response (eg flu, covid)

the immune response is weak so we need 3rd line treatment to manage viral infection

improve overall immune response

Question 15

How does tocilizumab work?

Answer 15

• monocloncal Ab
• blocks IL-6 receptor (pro inflam cytokine) → block cascade of inflamamtory response
• used for pro-inflam AI disease eg RA
• downregulates pro-inflam response to viral infection too

Question 16

Why is post exposure prophylaxis recommended for COVID, Chickenpox, Ebola?

Answer 16

• Vaccination not available.
• contra-indicated (chickenpox and pregnant women, immunocompromised).
• Not sure if vulnerable patients exposed to COVID-19 are at present prescribed antivirals or monoclonal antibodies if they are vaccinated
• Also for EBOV - vaccine that is not widely used and does not protect 100%.
• High case fatality rate for those infected with EBOV - risk not worth it, so given mAB or convalescent serum where available.
• Chickenpox very high risk to pregnant woman not previously vaccinated or not naturally infected before. Again, immunoglobulins given.

Question 17

What is Post-Exposure Prophylaxis (PEP)?

Answer 17

PEP (post-exposure prophylaxis) means taking a combination of drugs to prevent HIV after a possible exposure.

PEP should be used only in emergencies and must be started within 72 hours after a recent possible exposure to HIV.