Mechanism of Antivirals

Question 1

Describe the concepts of selective toxicity in relation to antivirals

[Concepts of selective toxicity in relation to viral infections]

Answer 1

*Target protein in virus, not infected cell (if possible)
*Due to the differences in structure and metabolic
pathways between host and pathogen

Question 2

Describe the mechanisms of action of several common antivirals: include anti-HIV agents, acyclovir, anti-flu drugs, and direct-acting antivirals

[Common examples of anti-viral drugs: e.g. flu, HIV, HepB, and HepC; herpesviruses]

Answer 2

Acyclovir [HSV, VZV, CMV/EBV] = inhibit nucleic acid polymerisation, requires two viral enzymes to be cleaved into active form
* HAART = Highly Active Anti Retroviral Therapy
* Amantadine = blocks low pH endosome dependant coating on M2 [influenza]
* Ribavirin/HCV inhibitors = prevent dsDNA => reverse transcriptase from HIV genome
HCV
- NS5A: blocking replication, complex formation and assembly
- NS5B: polymerase inhibitors preventing vision assembly
- NS3/4: ns3/4 protease inhibitors = no translation and procession of poly proteins [in prep for assembly and leaving host]

Question 3

Associate anti-viral agents with a particular target or life-cycle stage during viral replication

[Consideration of potential targets for antivirals]
[Generalised life cycles of viruses as obligate intracellular organisms]

Answer 3

• Preventing virus adsorption onto host cell
• Preventing penetration
• Preventing viral nucleic acid replication (nucleoside analogues)
• Preventing maturation of virus
• Preventing virus release

Question 4

Explain the basis for resistance to anti-viral agents with at least one example

[Concepts of anti-viral resistance]

Answer 4

HERPES R+
- two enzymes/mechanisms = TK mutation/CDP kinase mutation => R+
- immune competent = low load = effective in acyclovir treatment

HAART => targets HIV
- anti-reverse transcriptase inhibition:(nucleoside looking DNA base therefore r.t incorporates = DNA chain termination = no genome replication
- protease
- integrase inhibition
- fusion inhibition
- HIV high mutation rate => easy drug R+ development => combination HAART therapy

INFLUENZA R+
- only point mutations required for R+

Question 5

Describe the use of antivirals as prophylaxis agents for pre-and post-exposure to HIV

[Concepts of use of antivirals in pre-and post-exposure prophylaxis]

Answer 5

POST-EXP: 72 hours post exposure
- 2 NRTI (nucleotide reverse transcriptase inhibitors) + integrase inhibitor [for 28 days]

PRE-EP: combination NRTI’S + emtricitabine [guanosine analog] + tenofovir [adenosine analog]
- gets incorporated into chain. due to nucleotide structure
incorporation = chain termination

POST EXPOSURE PROPHYLAXIS: treating post infection effective
- contamination
- blood borne disease
- (sanitation and ppe