Nine Existing Drugs Reduce SARS-CoV-2 Viral Load in Cell-Based Study

A new study by researchers at the University of Manchester suggests that existing FDA-approved drugs may be suitable for repurposing as prophylactics, or for use in combination with vaccine therapy, to ward off COVID-19.

COVID-19: A need for effective drugs

Across the globe, the rollout of several different COVID-19 vaccines is helping to protect populations from contracting SARS-CoV-2 and becoming seriously ill. However, worldwide immunity to the virus has not yet been achieved. Therefore, therapeutic strategies to treat COVID-19 are still very much needed, should infection occur.

Since the outbreak of SARS-CoV-2, substantial efforts have been made in the field of drug discovery to identify safe and efficacious drugs to treat COVID-19. Despite these efforts, the number of drugs that have received authorization for use in COVID-19 patients is limited.

Increased attention has been placed on the possibility of repurposing or repositioning existing medications that are approved by regulatory authorities, such as the US Food and Drug Administration (FDA), for COVID-19. “Large proportions of the world’s population remain at risk of contracting COVID-19 as they wait to be vaccinated. The identification of safe and easily distributed medications that can target the different stages of virus infection and replication could reduce the spread of SARS-CoV-2 and reduce the cases of COVID-19," Professor Karl Kadler from the Wellcome Centre for Cell-Matrix Research at the University of Manchester told Technology Networks.

Screening existing drugs for COVID-19 

Kadler is part of the research team behind a new study published in PLoS Pathogens that screened 1971 FDA-approved drugs – that have made it through the lengthy drug development process and are licensed to treat other indications – to identify those that could be repurposed for application in COVID-19. 

To perform their screen, the team created a “traceable” version of the SARS-CoV-2 virus by replacing a sequence encoding a viral accessory protein with one that encodes nanoluciferase – an enzyme which fluoresces in the presence of its substrate and remains detectable even at very low levels.

This approach enabled them to quantify the viral load across a number of different human cell types, including hepatocytes (liver cells) and various cells within the kidney including proximal tubule cells and glomerulus cells. The researchers evaluated how well each of the cell types were able to be infected with SARS-CoV-2 and support its replication, before performing the drug screen. The compound library included antivirals, antibiotics, calcium ion channel inhibitors and drugs that modify dopamine and estrogen receptors.

By applying specific stringent criterion, the team was able to identify nine drugs from the screen that could reduce the fluorescently tagged SARS-CoV-2 virus in the cell cultures. "The drugs include ebastine (approved by the FDA for the treatment of Pneumocystis jirovecii pneumonia), and vitamin D3, which is available from health food stores and online, and could prove powerful additions to the treatment of COVID-19 in early stages of the disease or used prophylactically," Kadler noted.

The authors emphasize in the paper that, while many more compounds were able to slow virus replication prior to infection with the virus, they were not able to reduce viral load in cells that were pre-infected with SARS-CoV-2.

The appeal associated with repurposing existing FDA-approved drugs for application in COVID-19 is that it may reduce the timeframe for therapeutics to be made available for patients. "As these drugs are FDA-approved and with safe dosimetry already established for use in patients, clinical trials could be initiated for these drugs within a relatively short time frame," the authors write in the paper.

In addition, because these drugs are already licensed to treat other indications, they will likely have a robust production process, information will be available regarding storage requirements and distribution, and development costs will be known.  

Not an alternative to existing COVID-19 treatments or vaccination programs

Kadler and team are keen to emphasize that this work is preclinical, meaning that the results may not translate from the human cells in a laboratory to human patients with COVID-19. "It should be noted that these drugs are not alternatives to existing COVID-19 treatments or vaccination programs," he said. The teams' next steps are to explore whether the drugs identified in this study are effective in preventing humans from contracting the disease.

Professor Karl Kadler was speaking to Molly Campbell, Science Writer and Laura Lansdowne, Managing Editor at Technology Networks.

Reference: Pickard A, Calverley BC, Chang J, et al. Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells. PLoS Pathog. 2021;17(9):e1009840. doi: 10.1371/journal.ppat.1009840.