Tapeworm Drug Niclosamide Shows Strong Antiviral Effect as Potential New Treatment for COVID-19

Viral replication depends on host cell machinery and the use of the host’s molecular building blocks. In order to avoid detection by the immune system, viruses also have to ensure that they can evade cellular surveillance systems. To do this, they manipulate various processes in the infected host cell – and every virus pursues a different strategy.

This is why the researchers investigated the way in which SARS-CoV-2 reprograms host cells for its own benefit. Their key finding was as follows: The new coronavirus slows down the cell’s own recycling mechanism, a process known as autophagy. The purpose of this ‘auto-digestion’ mechanism is to enable the cell to dispose of damaged cell materials and waste products while recycling usable molecular building blocks for incorporation into new cellular structures.

When results from the study suggested that the recycling mechanism might be a potential target for COVID-19 therapy, the researchers tested whether substances which induce cellular recycling also reduce the replication of SARS-CoV-2 inside infected cells. Interestingly, the researchers found four substances which proved effective - all of them already in use in humans. These included the polyamine spermidine, an autophagy-enhancing metabolite which is produced in all human cells and by bacteria in the human gut. It occurs naturally in foods such as wheat germ, soya, mushrooms, and mature cheese and is freely available as a food supplement. When the researchers added spermidine to cells infected with SARS-CoV-2, this resulted in an 85% reduction in the numbers of virus particles produced. Similar results were produced by spermine, another polyamine which occurs naturally in the body. This derivative of spermidine was found to reduce viral replication by more than 90% in human lung cells and in a human gut model comprising clusters of cells known as ‘organoids’.

The third substance to prove effective against SARS-CoV-2 was the ‘AKT inhibitor’ MK-2206. The substance is currently at the clinical trial stage and undergoing testing for its tolerability and efficacy against a range of different cancers. In the current study, MK-2206 reduced the production of infectious SARS-CoV-2 virus by approximately 90%. It did so at plasma concentrations which had already been achieved during a previous study. The most pronounced antiviral effect was associated with niclosamide, which the researchers had shown to be effective against the MERS coronavirus during an earlier study. The tapeworm drug was found to reduce the production of infectious SARS-CoV-2 particles by more than 99%. The researchers will now conduct a study to test the safety, tolerability, and efficacy of niclosamide combined with camostat (another licenced drug) in patients recently (within the last few days) diagnosed with COVID-19.

“Niclosamide showed the strongest effect in our cell culture-based experiments. What is more, it has been licensed for use against tapeworm infections in humans for a very long time and is well tolerated at potentially relevant doses,” said PD Dr. Marcel Müller of Charité’s Institute of Virology who led the team of researchers. “Out of the four new candidate substances, we consider it to be the most promising one. This is why we are now conducting a clinical trial at Charité to test whether niclosamide might also have a positive effect on people with COVID-19.”

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