6.1 Antimicrobial agents (anti-virals, retrovirals fungals & helmintics)

Question 1

Why are viruses more difficult targets than bacteria?

When are they most vulnerable but what does this mean for their toxicity?

Answer 1

Because they mutate rapidly

They’re most vulnerable during reproduction, but because many use the host cell organelles/enzymes to do this the antiviral compounds are often as toxic to the host as they are to the virus

Question 2

Name the 5 main categories that antivirals are classified in

Answer 2

1) DNA polymerase inhibitors
2) mRNA synthesis inhibitors
3) Neuraminidase inhibitors; prevents of the release of virus from the cell surface
4) Immunomodulators; can minimize the viral effect
5) Viral penetration and uncoating inhibitors (no longer used as antivirals)

Question 3

Give 3 examples of DNA Polymerase Inhibitors and their function

Answer 3

Purine Analogues: Acyclovir, Ganciclovir, Cidofovir

Pyrimidine Analogues: Idoxuridine, Trifluridine

Non- Nucleosides: Foscarnet

Question 4

Give 2 examples of mRNA Synthesis Inhibitors

Answer 4

Ribavirin

Fomivirsen

Question 5

Give 2 examples of Neuraminidase Inhibitors

Answer 5

Prevents the release of virus from the cell surface

Oseltamivir

Zanamivir

Question 6

Give 2 examples of Immunomodulators

Answer 6

can minimize the viral effect

Interferons

Palivizumab

Question 7

What is a retrovirus and give one example

What is the main mechanism of action for anti-retroviral drugs?

Answer 7

A retrovirus is a RNA virus that inserts a copy of its genome into the DNA of a host cell.

Inside the host cell cytoplasm, the virus uses its own reverse transcriptase to produce DNA from its RNA genome (reverse of the usual pattern- “retro”).

The new DNA is then incorporated into the host cell genome by an integrase enzyme

Example HIV

Antiretroviral drugs target this process

Question 8

What are the 4 main classes of anti-retroviral drugs and what does each target?

Answer 8

1) Nucleoside reverse transcriptase inhibitors (NRTIs): inhibit translation into DNA
* NNRTIs- non-nucleoside reverse transcriptase inhibitors
2) Protease inhibitors (PIs): proteases are important in the retroviral life cycle
3) Fusion inhibitors: inhibit entry into the cell
4) Integrase inhibitors (inhibiting viral DNA from being incorporated into the genome)

Question 9

Give 2 examples of NRTIs and 2 examples of NNRTIs

Answer 9

NRTIs

• Zidovudine
• Stavudine
• Lamivudine
• Didanosine
• Abacavir

NNRTIs

• Nevirapine
• Efavirenz

Question 10

Give 2 examples of protease inhibitors (PIs)

Answer 10

• Lopinavir
• Ritonavir
• Nelfinavir
• Saquinavir-HGC
• Indinavir
• Fosamprenavir

Question 11

Give one example of a fusion inhibitor

Answer 11

Enfuvirtide

Question 12

Give one example of an integrase inhibitor

Answer 12

Raltegravir

Question 13

Is COVID19 a retro-virus?

Give a potential anti- viral targets for thhis

Answer 13

NO!!

Within the spike region of COVID19 is a cleavage site that is optimised to bind to the human ACE II receptor. These spike also increases the stability of binding and entry into human cells

If we coud create an antibody generated against these receptors (spikes) it would stop them binding onto the human cell receptors

Question 14

Name 2 classes of drugs that are anti-fungals and state their mechanism of action

Answer 14

1) Echinocandins: inhibits synthesis of 1,3-ß- glucan resulting in fungal cell wall lysis
2) Flucytosine: Inhibits DNA Synthesis

Question 15

List 3 ways in which Ant-helmintics drugs may acts

Answer 15

May act by causing :

1) Paralyzing of parasite
2) Damaging worm leading to elimination by immune mechanisms
3) Interfere with metabolism of the worm

Question 16

Give 2 classes of drugs that are Anti-helmintics and state their MOA

Answer 16

1) Ivermectin: Immobilizes parasites by tonic paralysis of musculature by activating glutamate-gated Cl channels
2) Niclosamide: Inhibits oxidative phosphorylation