New COVID-19 drugs such as Gilead Sciences’ remdesivir have their limitations, stressing the need for additional therapeutic options. To accelerate the drug development process, scientists have been looking to repurpose existing medicines. Now, an international team has locked onto an old leprosy drug, clofazimine, as a promising candidate.
Treatment with clofazimine significantly reduced viral load and shedding in hamsters infected with SARS-CoV-2, the novel coronavirus behind COVID-19, researchers from Sanford Burnham Prebys Medical Discovery Institute and the University of Hong Kong reported in a new Nature study. It also showed a synergistic effect with remdesivir, which is approved by the FDA under the brand name Veklury for hospitalized patients.
The University of Hong Kong has launched a phase 2 study testing the combination of clofazimine and interferon beta for hospitalized COVID-19 patients. As an old oral drug that’s included in the World Health Organization’s List of Essential Medicines, clofazimine holds potential as an affordable COVID-19 treatment, the researchers suggested.
“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,” the study’s co-senior author, Sumit Chanda, Ph.D., said in a statement.
Clofazimine was first used to treat leprosy in 1969 and was initially approved in the U.S. in 1986. The antimycobacterial has also been recommended—though not officially approved—to treat multidrug-resistant tuberculosis.
The researchers first identified clofazimine, along with 20 other existing drugs, as a possible weapons against SARS-CoV-2 by screening a large library of more than 12,000 clinical-stage or FDA-approved compounds.
For the new study, the team tested clofazimine in hamsters either before or after the animals were infected with the coronavirus. They found the drug was able to suppress the ability of the virus to copy its genome, and it lessened the formation of virus plaques in the lungs. Further, less of the virus showed up in the feces of animals that got clofazimine, while remdesivir didn’t seem to suppress viral shedding from the gastrointestinal tract.
An analysis of the virus’s behavior showed clofazimine targeted multiple steps involved in SARS-CoV-2 replication. That included interfering with a process in which the virus uses its spike protein to fuse with and gain entry to target cells.
Hamsters treated with clofazimine also had decreased levels of IL-6 in their blood and less lung damage, suggesting the drug could control a potentially deadly inflammatory response seen in some COVID-19 patients known as a cytokine storm.
Interestingly, the combination of clofazimine and remdesivir seemed to have an even better ability to inhibit SARS-CoV-2 replication in lab dishes. In hamsters, even a low dose of the combo suppressed viral shedding in the animals’ noses, which wasn’t achieved by either drug alone, the researchers reported.
“The antiviral synergy between low-dose remdesivir and clofazimine significantly improved viral control, with reduced body weight loss, suppressed pulmonary virus titer, and nasal virus shedding, as well as decreased drug dosages,” the researchers said in the study.
Research groups from different parts of the world have been searching existing drug libraries for clues to novel COVID-19 treatments. Scientists at the Cleveland Clinic suggested the popular over-the-counter sleep aid melatonin might be a viable option after an artificial intelligence analysis of the clinic’s COVID-19 registry showed individuals who were taking melatonin were less likely to test positive for SARS-CoV-2.
And, by using computational screening tools, scientists at a research institute in the Chinese Academy of Sciences found evidence that Acrotech Biopharma’s chemotherapy Folotyn, or pralatrexate, could have an even stronger effect against COVID than does remdesivir.
The authors of the new clofazimine study suggested the drug may offer a low-cost option for treating COVID-19, and a phase 2 clinical trial prescribing it as an at-home treatment is expected soon. What’s more, the drug also showed it could inhibit the coronavirus behind MERS, indicating it may have pan-coronavirus activity and could play a role beyond the current pandemic.