COVID-19 preclinical drug development database

Identification of New Therapeutic Combinations for Clinical Trial against COVID-19 Through Repurposing of Drugs with Known Safety Profile.

King's College London

Added 14/07/2020 | Updated 14/07/2020

Project Details

Type of project

  • Tier 1: repurposing existing medicines

Therapeutic target

  • Preventing infection (prophylaxis or preventing cell entry)
  • Preventing virus replication in early disease

Type of supporting technology

Phase of project

  • AI or in silico design
  • High throughput screening

Modality (if can be disclosed)*

  • Small molecule

Molecular/cellular target (if known or can be disclosed)*

  • ACE2
  • SARS-CoV-2 main protease
  • SARS-CoV-2 Spike protein

Partner institutions/organisations

  • Public Health England
  • IQVIA

Key contact

Name: Dr Miraz Rahman

Email Address: miraz.rahman@kc.ac.uk

Phone Number: 07717312299

Key Collaborators:
Primary Investigator Primary Investigator: Dr Miraz Rahman, Reader in Medicinal Chemistry, Institute of Pharmaceutical Science, King's College London Co-Investigators: Professor Bob Hider, King's College London, Dr Vivian Auyeung, IPS, King's College London Dr Julia Tree, COVID-19 project leader, Public Health England Dr Sue Charlton, Scientific Lead, Medical Intervention Team, Public Health England Collaborators: Professor Tim Mant, co-lead Advanced Therapies and Experimental Medicine Cluster, NIHR Biomedical Research Cluster, King's College London and Vice President Medical Strategy, IQVIA. Professor Liz Allen, Vice President Early Clinical Development, IQVIA

Anticipated timeframe of future outputs

This research project is looking for the following:

Expanding in vivo testing capabilities in relevant models.

Further Details

Abstract or additional information (if available)*

Repurposing regulatory agency-approved drugs and experimental drugs with known safety profiles (compounds that have progressed to phase II clinical trials) provides an important repository of compounds that can be screened against a SARS-CoV-2 target to identify clinical candidates that can be fast-tracked to clinical development within the next 6 months. There has been a global attempt to identify proteins that could be targeted to treat SARS coronavirus as effective treatments for the new COVID-19 disease. The IPS team aim to target all three stages of viral infection - viral entry and fusion with host cells, viral replication and the immune response resulting in a cytokine storm - to develop a combination of repurposed drugs that can be fast tracked to clinical development. IPS has partnered with Public Health England to achieve this. The IPS team is working with the crystal structures of the docking interface of spike (S) protein and host enzyme ACE2 (critical for viral entry), the main protease of SARS-CoV-2 and NSP15 ribonuclease protein (critical for viral replication) and dual targeting agents that can suppress a cytokine storm while also inhibiting viral replication. In addition, the IPS and PHE team propose to use iron chelators that work on lysosomes as part of the combination. Lysosomal iron content is vital for viral entry and initial establishment within the host cells. The Rahman Lab curates a 13,500 library of FDA approved drugs and carried out in silico screening against these targets. We identified 50 priority compounds that will be fast-tracked to in vitro cell-based SARS-CoV-2 screening at the PHE lab, to identify the most suitable combinations to carry out in vivo efficacy studies in a ferret model of SARS-CoV-2 infection at PHE. Once suitable combinations with in vivo efficacy have been identified, appropriate funding applications will be made to NIHR in partnership with PHE to carry out clinical trials of the candidate drugs. The project has been designed to take the drugs to clinical trials as soon as possible.

Published outputs (if available)*

A review article titled "Current Trends and Future Approaches in Small-Molecule Therapeutics for COVID-19" has been published by the research team in Current Medicinal Chemistry.