Identifying drugs to repurpose for COVID-19 Flashcards
Treatments for onset symptoms of COVID
Immune based prohalaxis – COV 2 vaccines/ antibodies
Treatment for fever/influenzas stage of COVID
Antiviral agents – prevent viral replication
Treatment for dyspnoea stage
Immune based therapies e.g. cytokine blockers
Life cycle of SARS COV 2
SARS COV2 docks onto ACE 2 receptor + fuses with cell membrane which allows entry into cell
• Proteases are important for making viral protein translation
• Virus replicates RNA and transcribes it
• Assembly of virus and release
What did the mendelian randomisation study tell us
Found drugs against interferon
Found ACE 2 receptors were a target
What did the High throughput screening study tell us
Investigated viral entry into cell
What did the molecular docking study tell us
Protease protein – crucial enzyme for virus
Anti-virals papers
Yang et al – high throughput screening
• Membrane fusion inhibitors – prevent viral entry into cell
Arun et al – molecular docking
• Viral protease inhibitors – inhibit protein translation and proteolytic activities
Graziano et al – Mendelian randomisation
• Entry inhibitors -target interaction between ACE-2 receptors and SARS Cov2 spike protein
• Viral replication inhibitors – inhibit replication and transcription of viral RNA
Graziano et al – Mendelian randomisation
• Viral replication inhibitor – inhibit replication and transcription of viral RNA
Challenges of drug repurposing? Scientific
- Computational methods only as good as study design and available datasets
- Most successful repurposed drugs come from observation
- May not be a drug for every target
- Repurposed drugs have less efficacy vs new target
- Drugs may need reformulation
Challenges of drug repurposing? Patents, regulatory and organisational hurdles
• Drug repurposing still requires significant investment
• Patents
collaboration between pharma, academia and biotech’s
