Managing early-stage COVID-19 with repurposed drugs

Managing early-stage COVID-19 with repurposed drugs
©Design Cells

A large-scale human genetic study has been used to identify drug targets that could help manage COVID-19 progression in the early stages of the illness.

A team of researchers from VA Boston Healthcare System, the University of Cambridge, EMBL’s European Bioinformatics Institute (EMBL-EBI), and Istituto Italiano di Tecnologia (IIT), has identified the IFNAR2 and ACE2 proteins as targets for potential drugs for the early management of COVID-19.

The research calls for clinical trials on drugs targeting both proteins to help prevent COVID-19 hospitalisation. The researchers note that prescribing these drugs after patients are diagnosed with COVID-19, but before their conditions require hospitalisation, could help minimise the symptoms and reduce the number of patients requiring critical care.

The research has been published in the journal Nature Medicine.

Identifying targets with computational analysis

The team used computational analysis methods and the ChEMBL bioactivity database to identify all protein-encoding genes that serve as targets for approved drugs or drugs in clinical development – identifying 1,263 druggable genes, which the researchers refer to as the ‘actionable druggable genome.’

The team investigated the prevalence of genetic variants in these druggable genes within two large genetic datasets from the VA’s Million Veteran Program and the COVID-19 Host Genetics Initiative, providing genetic evidence for drugs targeting the two proteins, ACE2 and IFNAR2.

Juan Casas, Physician Epidemiologist at the VA Boston Healthcare System, said: “When we started this project, most COVID-19 trials were being done on hospitalised patients. Very few treatments were being tested to give to patients early in the natural history of the disease.

“However, as the availability of testing against coronavirus increased, an opportunity opened to identify and treat COVID-19 patients before they progress to more severe forms of the disease that require hospitalisation.”

“Even as effective vaccines against the SARS-CoV-2 virus are being rolled out across the world, it is still very important to identify drugs we can use for COVID-19 treatment. Having a better understanding of which drugs we could use to prevent disease progression could save lives,” added Andrew Leach, Head of Chemical Biology at EMBL-EBI.

Anna Gaulton, ChEMBL Group Coordinator at EMBL-EBI highlighted that the ChEMBL database enabled the team to rapidly identify the protein targets of currently available drugs and compounds in late-stage clinical trials. “Cross-referencing this information with the results of the genetics analyses enables us to pinpoint potential new opportunities for drug repurposing for COVID-19 treatment,” she explained.

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