Ongoing efforts to identify medicines that could be rapidly repurposed against coronavirus.

Scripps Research teams are looking for anti-viral drugs that could be given to people already exposed to the novel coronavirus causing the COVID-19 pandemic. One priority is to test already approved drugs, or drugs with significant safety data in humans available, for activity against the novel coronavirus, known as SARS-CoV-2. These drugs could be made available to treat coronavirus patients on a much quicker timescale than novel therapies.

Calibr, the drug development division of Scripps Research, is leveraging a unique resource—the ReFRAME drug repurposing collection. With support from the Bill & Melinda Gates Foundation, Calibr compiled ReFRAME, the world’s leading collection of known drugs, comprising over 14,000 compounds that have been approved by the FDA for other diseases or have been extensively tested for human safety. Calibr also developed an open source database containing preclinical and clinical data on these compounds. Since information on the drugs’ therapeutic properties and safety is known, they can be screened and rapidly advanced into the clinic.

Since its creation in 2018, ReFRAME has been distributed broadly to nonprofit collaborators for global health and used to identify repurposing opportunities for a range of diseases. When the COVID-19 outbreak began, Calibr was able to mobilize ReFRAME quickly to begin searching for existing drugs and other compounds that might be repurposed against the coronavirus.

Previous studies showed that some of these molecules appear effective against closely related SARS and MERS coronaviruses, and now the teams are working together to test those same compounds against the novel SARS-CoV-2 virus. They are also screening for compounds in ReFRAME that prevent the virus from infecting cells in the first place.

In a separate project, Calibr scientists are collaborating with the Scripps Research lab of Dennis Burton, PhD, to screen for molecules that prevent SARS-CoV-2 from replicating after it enters cells. They hope that such a compound could serve as the basis for an antiviral therapy.

Calibr scientists are also screening for drugs that could augment the effectiveness of the Gilead drug remedesivir which is currently being tested in five COVID-19 clinical trials, as well as partnering with pharma companies to screen earlier stage antiviral drugs.

Since the outbreak began, Calibr has established collaborations to screen the ReFRAME library for potential coronavirus therapies with nine outside research teams, including US laboratories in Maryland, Massachusetts, New York, and Texas, as well as overseas labs in the UK, Germany, Belgium and Hong Kong. ReFRAME has been highlighted in the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation. Together, Calibr and the Gates Foundation are working to establish collaborations with the leading pharma companies to augment ReFRAME’s collection of antiviral compounds for future pandemic response.