During the global pandemic, many researchers have responded to the needs of patients severely afflicted with COVID-19 by repurposing existing therapies being developed to treat patients.  CIRM responded immediately to the pandemic and to researchers wanting to help by providing $5 million in emergency funding for COVID-19 related projects. 

One of these grants ($349,999), awarded to Dr. Vaithilingaraja Arumugaswami at UCLA, has aided a study that has singled out a compound that shows promise for treating SARS-CoV-2, the virus that causes COVID-19.

In the spirit of banding together to help patients severely affected by COVID-19, the project was a collaboration among scientists from UCLA and other universities in California, Delaware and Germany, as well as a German pharmaceutical company.

The compound is named berzosertib and is licensed by the company Merck KGaA in Darmstadt, Germany.  Prior to the pandemic, it was developed for potential use, in combination with chemotherapy, as a possible treatment for small-cell lung cancer, ovarian cancer, and other types of solid tumors.

The team screened 430 drugs from among the approximately 200,000 compounds in CNSI’s Molecular Screening Shared Resource libraries before zeroing in on berzosertib as the most promising candidate.  They limited their search to compounds that either had been approved, or are already in the process of being evaluated, for safety in humans.

In a press release from UCLA, Dr. Arumugawami explains the rationale behind screening a potential drug candidate.

“That way, the compounds have cleared the first regulatory hurdle and could be deployed for further clinical trials on COVID-19 faster than drugs that have not been tested in humans.”

The researchers, led by Dr. Arumugaswami and Dr. Robert Damoiseaux from UCLA, conducted a series of experiments using different cell types in lab dishes to look at how effective the compound was at blocking SARS-CoV-2 from replicating.  Unlike other approaches which attack the virus directly, targeting replication could help better address the ability of the virus to mutate. 

For this study, the team used cells from the kidney, heart and lungs, all of which are organs that the virus is known to attack. The researchers pretreated cells with berzosertib, exposed the cells to SARS-CoV-2, allowed 48 hours for infection to set in, and then evaluated the results.

The team found that the compound consistently stalled SARS-CoV-2 replication without damaging the cells. The scientists also tested the drug against SARS and MERS, both of which are other types of coronaviruses that triggered deadly outbreaks earlier in the 2000s. They found that it was effective in stopping the replication of those viruses as well.

In the same press release from UCLA, Dr. Damoiseaux expressed optimism for what these findings could mean as a potential treatment.

“This is a chance to actually find a drug that might be broader in spectrum, which could also help fight coronaviruses that are yet to come.”

The next steps for this research would be to explore the mechanism through which the compound blocks coronavirus replication.  Understanding this and conducting preclinical studies are both necessary before the compound could be tested in clinical trials for COVID-19.

The full results of this study were published in Cell Reports.

The study’s co-corresponding author is Ulrich Betz of Merck KGaA, Darmstadt, Germany; the company also provided partial funding and clinical-grade berzosertib for the research. Other co-authors are from UCLA, Cedars-Sinai Medical Center, UC Irvine, University of Delaware, the Leibniz Institute for Experimental Virology in Germany, Heidelberg University in Germany and Scripps Research Institute.

In addition to CIRM, the study was also funded by CNSI, the Broad Stem Cell Research Center, the David Geffen School of Medicine at UCLA, the National Eye Institute, and the Bill and Melinda Gates Foundation.