While much of the fanfare for getting the COVID-19 pandemic tamped down is currently going to vaccinations, other researchers continue to look for potential treatments for people who become infected with the SARS-C0V-2 virus. A portion of that work is spent scouring data of older, already approved drugs for other conditions that may have antiviral properties. New research out of Sanford Burnham Prebys may have found such a drug: clofazimine, a decades-old treatment for leprosy.
This work is published in Nature in the article, “Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.”
“Clofazimine is an ideal candidate for a COVID-19 treatment. It is safe, affordable, easy to make, taken as a pill, and can be made globally available,” said co-senior author Sumit Chanda, Ph.D., professor and director of the immunity and pathogenesis program at Sanford Burnham Prebys. “We hope to test clofazimine in a Phase II clinical trial as soon as possible for people who test positive for COVID-19 but are not hospitalized. Since there is currently no outpatient treatment available for these individuals, clofazimine may help reduce the impact of the disease, which is particularly important now as we see new variants of the virus emerge and against which the current vaccines appear less efficacious.”
Clofazimine, which was discovered in 1954, is FDA approved and on the World Health Organization’s List of Essential Medicines. The drug’s utility for COVID-19 was initially identified by screening more than 12,000 drugs from the ReFRAME drug library—one of the most comprehensive collections 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, with support from the Bill & Melinda Gates Foundation, with a goal of repurposing existing drugs to meet unmet clinical needs. Chanda’s team previously reported that clofazimine was one of 21 drugs effective in vitro, or in a lab dish, at concentrations that could most likely be safely achieved in patients.
In this study, clofazimine was found to inhibit viral spike-mediated cell fusion and viral helicase activity. In a hamster model of infection, prophylactic or therapeutic administration of clofazimine significantly reduced viral load in the lung and fecal viral shedding, and “also mitigated inflammation associated with viral infection.”
“The animals that received clofazimine had less lung damage and lower viral load, especially when receiving the drug before infection,” said co-senior author Ren Sun, PhD, professor at the University of Hong Kong and professor emeritus at the University of California, Los Angeles (UCLA). “Besides inhibiting the virus, there are indications that the drug also regulates the host response to the virus, which provides better control of the infection and inflammation.”
Clofazimine also worked synergistically with remdesivir, the current standard-of-care treatment for people who are hospitalized due to COVID-19, when given to hamsters infected with SARS-CoV-2. These findings suggest a potential opportunity to stretch the availability of remdesivir, which is costly and in limited supply.
Clofazimine was also able to reduce the replication of MERS-CoV, the coronavirus that causes Middle East Respiratory Syndrome (MERS), in human lung tissue. “Potentially most importantly, clofazimine appears to have pan-coronavirus activity, indicating it could be an important weapon against future pandemics,” said co-senior author Kwok-Yung Yuen, MD, chair of infectious diseases at the University of Hong Kong, who discovered the coronavirus that causes severe acute respiratory syndrome (SARS). “Our study suggests that we should consider creating a stockpile of ready-made clofazimine that could be deployed immediately if another novel coronavirus emerges.”
A Phase II trial evaluating clofazimine in combination with interferon beta-1b as a treatment for people with COVID-19 who are hospitalized is ongoing at the University of Hong Kong. Interferon beta-1b is an immunoregulator that is given as an injection and is currently used to treat people with multiple sclerosis.
“Our data suggests that clofazimine should also be tested as a monotherapy for people with COVID-19, which would lower many barriers to treatment,” said Chanda. “People with COVID-19 would be able to simply receive a regime of low-cost pills, instead of traveling to a hospital to receive an injection.”