COVID-19 preclinical drug development database

High throughput screening of approved drugs to search for inhibitors of SARS-CoV-2 Spike protein-induced cell-cell fusion

King's College London

Added 08/07/2020 | Updated 08/07/2020

Project Details

Type of project

  • Tier 1: repurposing existing medicines

Therapeutic target

  • Preventing virus replication in early disease
  • Preventing damage induced by virus-infected cells

Type of supporting technology

Phase of project

  • High throughput screening

Modality (if can be disclosed)*

  • Small molecule

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

  • SARS-CoV-2 Spike protein

Partner institutions/organisations

  • Imperial College London

Key contact

Name: Mauro Giacca

Email Address: mauro.giacca@kcl.ac.uk

Phone Number: +44 207 848 1309

Key Collaborators:
Professor Mauro Giacca Professor Juan Burrone Professor Ajay Shah Professor Wendy Barclay (Imperial College London)

Anticipated timeframe of future outputs

Further Details

Abstract or additional information (if available)*

COVID-19 is a unique disease with distinctive clinical characteristics, including extensive thrombosis, frequent diarrhoea and hyperinflammation, in addition to unexplained symptomatology. The pathological substrates for these characteristics remain largely elusive. We found that the lungs of patients with COVID-19 show the presence of infected pneumocytes with abnormal morphological characteristics and frequent multinucleation, a feature that depends on the presence of the viral Spike protein on the plasma membrane of the infected cells. Based on this information, we performed two high-content microscopy, high-throughput screenings with over ~3000 small molecules to search for approved drugs that inhibit Spike-driven syncytia formation. The two screenings converged on the identification of 83 drugs that markedly inhibited Spike-mediate cell-cell fusion, several of which belonged to defined pharmacological classes. After testing the effects of these drugs on infectious SARS-CoV-2, we focussed our attention on three drugs that were among the most effective at inhibiting Spike-induce syncytia and protecting the cells against virus-induced death.

Published outputs (if available)*

Relevant weblinks