Antivirals seminar

Question 1

What are antivirals?

Answer 1

Medicines that stop viruses from mulitplying.
Agents + drugs.

Question 2

Why do side effects occur and what are common side effects?

Answer 2

When antivirals target essential host factors.
Common:
Nausea, vomiting, allergic reactions, drowsiness, insomnia, heart problems, and dependence.

Question 3

What are the seven classes of antiviral agents?

Answer 3

• Neutralizing Ab
• Neutralizing recombinant human receptors
• Antigenic CRISPR/Cas systems
• IFNs
• Antigenic peptides
• Antigenic nucleic acid polymers
• Antigenic small molecules

Question 4

What does neutralizing Abs affect?

Answer 4

Virus attachment.
Secreted nAb bind viral spike protiens in the blood. Can be cell-bound

Convalescent plasma can be collected and transfused to new patient to block virus.

Can be monoclonal or have a broader range. mAbs are often too specific -> not good against novel mutations.

Question 5

What does neutralizing recombinant soluble human receptors affect?

Answer 5

Virus attachment.

Can engineer sequences on receptors that are specific against seq on virus receptors.
Example: soluble ACE2 receptor against SARS-CoV-2.
Can engineer them to e.g., enhance plasma half-life…

Question 6

What parts of the viral life cycle does antiviral CRISPS/Cas systems affect?

Answer 6

Viral gene expression and replication.
Recognize and destroy specific sequences in viral genome.

Can be used against e.g., herpesviruses to impair replication and clear latent virus infection (EBV, HCMV, HSV-1).

Question 7

What stages og the virus life cycle do IFNs affect?

Answer 7

Viral gene expression and replication.
Secreted by infected cell and work on the secreting cell itself or its neighbors. Bind extra-/ intracellular receptors to induce cellular pathways. Result in induction of interferon stimulated genes (ISGs), and the protein products directly inhibit viral gene expression and replication.

Question 8

What is the role of antiviral peptides during a virus infection?

Answer 8

Many functions but the main is to inhibit viral attachment:
- Inhibit virus binding to cellular receptors
- Virus destabilizers
- Virus entry inhibitors
- Endosome acidification inhibitors
- Fusion inhibitors
…

Question 9

What parts of the viral life cycle do antiviral nuncleic acid polymers affect?

Answer 9

Viral gene expression and replication.
Example: siRNA
dsRNA that blocks mRNA so that certain genetic information is not converted into proteins. Guides specific virus clearance by RNAi (Dicer, cut)

Question 10

Which stages of the virus life cycle do antiviral small molecules affect?

Answer 10

Several stages.
Example: be inserted as an alternative to a base during replication.
Influenza:
Endonuclease inhibitors
M2 ion channel inhibitors
NA inhibitors -> no release

Question 11

Why are antiviral drug combinations often used?

Answer 11

• Target broader range of viruses (including
  emerging)
• Slow down development of drug resistance
• Show synergistic effects
  
  • Reduced doze and minimized side effects
    of individual drugs

Question 12

What can be done to prepare for the next “virus x” pandemic?

Answer 12

Drug repurposing + drug combination.
Should identify safe antivurals with broad range of viral targets.

Can use “broad spectrum antibodies”, BSA.
- Combinations of BSAs to obtain synergistic
effects without detectable toxicity.
- Cover many viruses from same/different viral
families.
- Prevent development of drug resistant virus
variants

Question 13

Give an example of a broad-spectrum antiviral and its mode of action

Answer 13

Remdesivir - allow entry of ribonucleotide analog of viral RNA pol

IFNα
IFNβ

Ribavirin - guanosine (ribonucleic) analog used to stop viral RNA synthesis and viral mRNA capping, thus, it is a nucleoside analog.

Ganciclovir triphosphate - competitive inhibitor of dGTP incorporation into DNA. Inhibits vRNA pol more than cellular RNA pol