If the Sars coronavirus-2 penetrates a host cell, it converts the metabolism there so that the cell mainly produces new viruses. In order not to immediately attract the immune system’s attention, the virus also manipulates other processes in the cell. As a team led by the virologist Marcel Müller from the Berlin Charité and Nils Gassen from the Bonn University Clinic shows in a new article for “nature communications”, Corona inhibits the so-called autophagy, a kind of recycling system with which cells store building blocks that are no longer required rebuild new structures.
But this autophagy can be stimulated again, which can slow down the replication of the virus, the researchers write. Among other things, this works with the body’s own substances spermine and spermidine, with an experimental cancer drug MK-2206 and with the tapeworm drug niclosamide. The doctors now want to examine the latter in a clinical phase 2 study for effectiveness against Covid-19 and tolerability.
Spermidine: effective in cell culture, but self-medication is still not advisable
The researchers suspect that viruses are destroyed again during autophagy. To stimulate the process, they examined various substances in cell cultures infected with corona in the laboratory. First they used spermine and spermidine, two so-called polyamines, which occur in foods such as wheat germ, soy or mushrooms or are produced by the body itself. The name is derived from the fact that human sperm cells – the sperm – are particularly rich in spermidine.
When the researchers added spermidine to the infected cells, they produced 85 percent fewer infectious virus particles. In sperm, there were even 90 percent fewer viruses. “These clear effects of spermidine and especially spermine are of course encouraging on the one hand because fewer side effects are to be expected with the body’s own substances,” says virologist Marcel Müller. “However, we have worked with pure substances, which in this form are not suitable for medicinal ingestion. Spermidine in particular is only noticeably effective in cell culture at a very high concentration.”
Spermidine is also freely available as a dietary supplement. Nevertheless, Müller advises against treating yourself with spermidine before the researchers have clarified further questions in studies. This includes when in the event of an infection and in what way it might make sense to take it, “also because viruses use polyamines to multiply and the right dosage is therefore important,” says Müller. “The same applies to fasting, which can stimulate autophagy in the body: It is not clear whether Covid-19 patients would benefit from fasting, since the body needs a lot of energy for the immune reaction during an infection.”
Niclosamide even shows a 99 percent reduction in virus production
The experimental cancer drug MK-2206, which is currently being investigated against various tumors in clinical studies, has also proven to be 90 percent effective. According to Müller, it could be another candidate against Sars-CoV-2. However, the tapeworm remedy niclosamide performed best. It was able to reduce the production of coronaviruses in cell culture by 99 percent. “Niclosamide has shown the strongest effect in our cell culture studies and has also been a drug that has been approved for tapeworm infections for years and is well tolerated in potentially effective doses. We consider it the most promising of the four new drug candidates,” says Müller.
Therefore, doctors at the Berlin Charité now want to test in a phase 2 study with recently infected Covid-19 patients whether niclosamide in combination with the drug Camostat can improve the course of the infection. To do this, the clinic is looking for participants.