An international team of scientists have pointed out in a Nature study that as many as 21 existing drugs have the potential of stopping Covid-19 in its tracks and treating patients.
The researchers looked at one of the world’s largest collections of known drugs for their ability to block the replication of SARS-CoV-2, and reported 100 molecules with confirmed antiviral activity in laboratory tests. Of these, 21 drugs were determined to be effective at concentrations that could be safely achieved in patients. Notably, four of these compounds were found to work synergistically with remdesivir, a current standard-of-care treatment for COVID-19.
For the study researchers performed extensive testing and validation studies, including evaluating the drugs on human lung biopsies that were infected with the virus, evaluating the drugs for synergies with remdesivir, and establishing dose-response relationships between the drugs and antiviral activity.
Of the 21 drugs that were effective at blocking viral replication, the scientists found:
- 13 have previously entered clinical trials for other indications and are effective at concentrations, or doses, that could potentially be safely achieved in COVID-19 patients.
- Two are already FDA approved: astemizole (allergies), clofazamine (leprosy), and remdesivir has received Emergency Use Authorization from the agency (COVID-19).
- Four worked synergistically with remdesivir, including the chloroquine derivative hanfangchin A (tetrandrine), an antimalarial drug that has reached Phase 3 clinical trials.
The researchers are currently testing all 21 compounds in small animal models and “mini lungs,” or lung organoids, that mimic human tissue. If these studies are favorable, the team will approach the U.S. Food and Drug Administration (FDA) to discuss a clinical trial(s) evaluating the drugs as treatments for COVID-19.
The drugs were first identified by high-throughput screening of more than 12,000 drugs from the ReFRAME drug repurposing collection—the most comprehensive drug repurposing collection of compounds that have been approved by the FDA for other diseases or that have been tested extensively for human safety.
ReFRAME was created by Calibr, the drug discovery division of Scripps Research, under the leadership of President Peter Shultz, Ph.D., with support from the Bill & Melinda Gates Foundation. It has been distributed broadly to nonprofit collaborators and used to identify repurposing opportunities for a range of disease, including tuberculosis, a parasite called Cryptosporidium and fibrosis.