Clofazimine inhibits coronaviruses including SARS-CoV-2, study finds

As the coronavirus disease (COVID-19) pandemic continues, scientists race to develop or find effective treatments to stem its spread. At the same time, health experts and scientists continue to determine which existing drugs could be repurposed to treat COVID-19.

Researchers at the University of Hong Kong found that Clofazimine, a lipophilic antimicrobial riminophenazine dye used in combination with agents like rifampicin and dapsone to treat leprosy, inhibits coronaviruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease.

The study, a manuscript accepted for publication in the journal Nature, highlights the potential of drug repurposing, wherein drugs approved for treating other diseases are used to treat current outbreaks.

What is Clofazimine?

Clofazimine, sold under the brand name Lamprene, is a bright-red dye initially described in 1957 to treat leprosy or Hansen’s disease, a chronic infectious disease caused by the infective agent, Mycobacterium leprae.

Leprosy mainly affects the skin, mucosal surfaces, upper respiratory tract, eyes, and peripheral nerves.

Clofazimine is indicated for the treatment of lepromatous leprosy, including lepromatous leprosy and dapsone-resistant lepromatous leprosy complicated by erythema nodosum leprosum.

The study

The study demonstrated that the leprosy drug clofazimine, Food and Drug Administration (FDA)-approved and included in the World Health Organization’s List of Essential Medicines, exhibited potent antiviral activity against SARS-CoV-2.

The drug also prevented the exaggerated inflammatory response tied to the severe COVID-19. The results were based on the findings of a Phase II study that evaluated Clofazimine as an at-home treatment for SARS-CoV-2 infection.

To arrive at the study findings, the researchers tested Clofazimine in Syrian hamsters infected with SARS-CoV-2. They found that the drug suppressed the viral load in the lungs, reducing lung damage and preventing a potentially-fatal complication, a cytokine storm. Cytokine storm is characterized by an overwhelming inflammatory reaction of the body against SARS-CoV-2.

Apart from the amount of the virus in the lungs, the drug also reduced viral shedding, a potentially contagious condition when the virus replicates in the body and is released into the environment. The reduced viral shedding was seen in nasal and fecal samples of the hamsters treated with the drug.

“Overall, clofazimine exhibited broad-spectrum anti-CoV efficacy, and antagonized both SARS-CoV-2 and MERS-CoV replication in the human primary cell and ex vivo lung models,” the team noted in the study.

Clofazimine works by blocking viral entry into cells and altering ribonucleic acid (RNA) replication. In the study, the drug reduced the replication of another coronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV-2), in human lung tissue.

The drug appears to have a pan-coronavirus activity, which means it could be used not only for SARS-CoV-2 but also for other coronaviruses that may threaten global public health.

Currently, the Phase 2 trial of Clofazimine with interferon beta-1b for treating people with COVID-19 is ongoing at the University of Hong Kong.

Clofazimine and remdesivir combination

Remdesivir was the first drug approved by the FDA for use in adults and children 12 years old and above for treating COVID-19 requiring hospitalization. The drug should only be administered in a hospital or in a healthcare setting capable of providing acute care.

The researchers also found that co-application of Clofazimine and remdesivir impacts SARS-CoV-2 replication. The drug can be used to stretch the availability of remdesivir, which is costly and has limited supply. Subsequently, Clofazimine exhibited not only potent synergy in terms of viral load but also limited viral replication and reduced viral shedding in the nasal wash, which was not achievable with therapeutic remdesivir or Clofazimine alone.

“Taken together, 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 team added.

Repurposing drugs to combat SARS-CoV-2 infection is crucial as the pandemic continues to wreak havoc globally. To date, there are more than 123 million reported infections from SARS-CoV-2 and over 2.71 million deaths attributed to COVID-19 disease. Of these, over 69 million people have already recovered.

Source:
Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.

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