Are you using a repellent for SARS-CoV-2?

Researchers at the German Center for Infection Research (DZIF) in Charite-Universitätsmedizin Berlin and the University of Bonn have investigated how SARS-CoV-2 can reprogram host cell metabolism for overall benefit.According to their report Nature Communications, Researchers have been able to identify four substances that inhibit SARS-CoV-2 replication in host cells. Spermine and spermine, substances that are naturally present in the body. MK-2206, anti-cancer drug; niclosamide, streak drug. Charite is currently conducting tests to determine if niclosamide is also effective against human COVID-19.

Viral replication depends on the mechanism of the host cell and the use of the host’s molecular building blocks. To evade detection by the immune system, the virus also needs to ensure that it can evade the cell surveillance system.To do this, they operate various infected processes Host cell— And every virus pursues a different strategy.This is SARS-CoV-two reprogram hosts led by a team of researchers led by PD Dr. Marcel Müller of the Charité’s Institute of Virology and Dr. Nils Gassen of the University Hospital Bonn (UKB) Psychiatry and Psychotherapy Clinic and Outpatient Clinic. cell For its own benefit. Their important discoveries are: The new coronavirus slows down the recycling mechanism of the cells themselves, a process known as autophagy. The purpose of this “auto-digestion” mechanism is to allow cells to dispose of damaged cell material and waste products while recycling the molecular building blocks that can be used to incorporate them into new cell structures.

“In our study, SARS-CoV-2 uses cellular components for its own benefit while at the same time deceiving cells by simulating nutrient-rich conditions, thereby recycling cells. I was able to show that I would delay it, “explains first. Author Dr. Gassen. As part of this study, researchers conducted a detailed analysis of SARS-CoV-2 infected cells and lung tissue in COVID-19 patients to study cell metabolism and processing of molecular signals. “SARS-CoV-2 may be used to avoid cell disintegration. After all, viruses are also subject to autophagy,” said DZIF, the last author of the study. Researcher PD Dr. Müller adds. “The same reprogramming strategy was also used in the MERS coronavirus, and its autophagy-inhibiting effect was demonstrated over a year ago, but in stark contrast, it induces autophagy. There are other coronaviruses, which mainly infect animals. “

When the results of the study suggest that the recycling mechanism may be a potential target for COVID-19 therapy, researchers ask whether substances that induce cell recycling also reduce SARS-CoV-2 replication in infected cells. I tested it. Interestingly, researchers have discovered four substances that have proven effective. They are all already used by humans. These contained polyamine spermidine, an autophagy-enhancing metabolite produced by all human cells and bacteria in the human intestine. It is naturally found in foods such as wheat germ, soybeans, mushrooms and aged cheese and is available free of charge as a dietary supplement. When researchers added spermidine to cells infected with SARS-CoV-2, the number of viral particles produced was reduced by 85%. Similar results were produced by another naturally occurring polyamine in the body, spermine. This derivative of spermidine has been found to reduce viral replication by more than 90% in human intestinal models containing human lung cells and clusters of cells known as “organoids”.

“The obvious effects of spermidine, especially spermine, are certainly encouraging, partly because naturally occurring substances in the body are less likely to cause side effects,” said PD Dr. Müller. I will. “That said, we used these substances in pure form, which are not suitable for medical use. In particular, spermidine needs to be used in relatively high concentrations to achieve a significant effect in cell culture. Therefore, many questions need to be answered. Before considering polyamine as a potential treatment for COVID-19: sufficient to inhibit viral replication in the respiratory tract when used in the body Is it possible to achieve high concentrations? And if so: Is infection recommended before or during administration? Are there any side effects? Still, our findings from cell cultures include animal models. A good starting point for research. Self-treatment is not recommended. One of the reasons is that the virus uses polyamines to promote replication; therefore, the correct dose is important. The same is true for fasting. This is true and may stimulate the body’s autophagy process. Given that the body needs energy to initiate an immune response, is fasting recommended for patients infected with SARS-CoV-2? I’m still not sure. “

The third substance that proved to be effective against SARS-CoV-2 was the “AKT inhibitor” MK-2206. The substance is currently in clinical trials and is being tested for its tolerability and efficacy against a variety of cancers. In the current study, MK-2206 reduced the production of infectious SARS-CoV-2 virus by about 90%. This was done at plasma concentrations already achieved in previous studies. “Based on our data, I consider MK-2206 to be an interesting treatment candidate for COVID-19. This is after careful analysis of the risks and benefits. Clinical trial“Dr. Muller of PD explains.

The most prominent antiviral effect is associated with niclosamide, and previous studies have shown that it is effective against MERS coronavirus. Tapeworm drugs have been found to reduce the production of infectious SARS-CoV-2 particles by more than 99%. “Niclosamide has shown the strongest effect in our cell culture-based experiments. In addition, it has been approved for use against human tapeworm infections for a very long time and at potentially appropriate doses. It’s well tolerated, “says Dr. PD Muller. “Of the four new candidate substances, we consider it to be the most promising. This is a clinical trial at Charite to test whether niclosamide also has a positive effect on people with COVID-19. I am pleased with this development. This is how quickly discoveries from basic research can be made when research and clinical practice are closely linked and work together in an efficient manner. Indicates whether it will reach the patient. “

The Phase II clinical trial, entitled “NICCAM,” is led by Dr. Martin Witzenras, Deputy Director of Infectious Diseases and Respiratory Medicine in Charite. This study tests the safety, tolerability, and efficacy of a combination of niclosamide and camostat (another approved drug) in patients who have recently been diagnosed with COVID-19 (within the last few days). .. This survey is currently recruiting participants.