Can they end the pandemic?

A team of scientists has identified 21 existing drugs that could put an end to the replication of SARS-CoV-2, the virus that causes COVID-19

ANature study authored by a global team of scientists and led by Sumit Chanda, Ph.D., professor at Sanford Burnham Prebys Medical Discovery Institute, has identified 21 existing drugs that stop the replication of SARS-CoV2, the virus that causes COVID-19.

The scientists analysed 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-ofcare treatment for COVID-19.

“Remdesivir has proven successful at shortening the recovery time for patients in the hospital, but the drug doesn’t work for everyone who receives it. That’s not good enough,” says Chanda, director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study. “As infection rates continue to rise in America and around the world, the urgency remains to find affordable, effective, and readily available drugs that can complement the use of remdesivir, as well as drugs that could be given prophylactically or at the first sign of infection on an outpatient basis.”

In the study, the research team 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 Authoriza

tion 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. “This study significantly expands the possible therapeutic options for COVID-19 patients, especially since many of the molecules already have clinical safety data in humans,” says Chanda. “This report provides the scientific community with a larger arsenal of potential weapons that may help bring the on-going global pandemic to heel.” 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 favourable, 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.

“Based on our current analysis, clofazimine, hanfangchin A, apilimod and ONO 5334 represent the best near-term options for an effective COVID-19 treatment,” says Chanda. “While some of these drugs are currently in clinical trials for COVID-19, we believe it’s important to pursue additional drug candidates so we have multiple therapeutic options if SARSCoV-2 becomes drug resistant.”