COVID-19 enlarges cells in our body and promotes virus hijacking

Diagram of SARS-CoV-2 virus particles entering cells. Particles penetrate cell membranes, which are made up of two layers of lipids. The PNNL-OHSU team has shown how lipids are the key to the ability of viruses to replicate. (Illustration by Michael Perkins / Pacific Northwest National Laboratory)

The virus that causes COVID-19 hijacks the body’s fat processing system on a large scale, creating a cell reservoir of fat that empowers the virus to take over the body’s molecular mechanisms and cause disease. Scientists at the Oregon University of Health Sciences and the Pacific Northwest National Laboratory of the Ministry of Energy have discovered the important role of fat in SARS-CoV-2 and then used weight loss drugs and other fat-targeting compounds to intracellularly use it. I tried to stop the virus. culture. When the fat fuel was shut off, the virus stopped replicating within 48 hours.

Researchers who announced the survey results Nature CommunicationsNote, the result is a cell culture, not a human. More research remains to see if such compounds are promising for people diagnosed with COVID. But scientists call this research an important step in understanding the virus.

Dr. Fikadu Tafes (Osu)

“This is an exciting job, but it’s the beginning of a very long journey,” he said. Dr. Fikadu Tafes, Corresponding author of the study and assistant professor of molecular microbiology and immunology at OHSU School of Medicine. “There are interesting observations, but there is still much to learn about the mechanism of this disease.”

Fat as fuel

The team set out to study based on the observation that people with high obesity indexes and conditions such as cardiovascular disease and diabetes are more sensitive to this disease.

The team studied the effects of SARS-CoV-2 on more than 400 lipids or fats in two different human cell lines. Scientists have discovered significant changes in lipid levels, with some fats increasing 64-fold. In one cell line, nearly 80% of fat was changed by the virus. Second, the level has changed slightly more than half.

The most affected lipid is triglyceride, a small packet of fat that most patients try to minimize. Triglycerides are very important to our health and allow us to store energy and maintain a healthy intracellular membrane.

These oily fat masses also proved to be important for the COVID-19 virus.

Dr. Jennifer Kyle (PNNL)

“Lipids are an important part of every cell. They literally connect us by keeping our cells intact and are the main source of energy for our body,” he said. Dr. Jennifer Kyle, A PNNL biomedical scientist who specializes in measuring lipids. “They are attractive targets for the virus.”

When energy is needed, cells break down triglycerides into useful sources. These are the three fatty acids found in each triglyceride molecule.

The team discovered that SARS-CoV2 does not simply increase the amount of intracellular triglycerides. The virus also alters many of our fat processing systems, altering the body’s ability to use fat as fuel.

Scientists went a step further to investigate the effects of the virus on lipid levels in 24 of the 29 proteins. The painstaking laboratory work was done at OHSU, after which the cells were sent to PNNL for measurement and analysis.

Reduction of fuel supply

The team identified a handful of viral proteins that have a particularly strong effect on triglyceride levels. Based on the findings, the team searched the database and identified some compounds that could ruin the body’s fat processing system. Some have proven effective in preventing the virus from replicating in the laboratory.

Orlistat, an approved weight-loss drug, is a lipase inhibitor that prevents triglycerides from breaking down into fatty acids and has stopped viral replication. An compound known as GSK2194069 also blocked the virus. These and other compounds worked for all SARS-CoV2 variants tested (alpha, beta, gamma, and delta).

“When a virus replicates, it requires a continuous supply of energy. More triglycerides can provide that energy in the form of fatty acids. But how the virus makes these lipids. I don’t know exactly if it will be used in an advantageous way, “says Tafes, a team who saw changes in lipids as a result of the dicavirus and HIV.

This study is the result of ongoing collaboration between OHSU and PNNL. Institution four years ago Release What is currently known Pacific Northwest Biomedical Innovation Joint Institute, Or PMedIC. Scientists and physicians work together to combine basic science and clinical experience to explore illnesses and develop innovative therapies.

This effort combines PNNL’s basic research, especially its ability to measure and interpret the levels of molecules such as lipids, proteins and metabolites, with its extensive experience in OHSU’s science and human illness.Collaboration has produced several research projects and produced related results. Zika virus, kidney failure When Alzheimer’s disease..

The authors of the PNNL paper are: Kyle, Thomas Mets, Lisa Brammer When Yon Yon Lee.. The author of OHSU is Tafesse, the lead author Scottish Farley, Hans Layer, Jules Waynestein, Timothy Bates When Karsten Schultz..

This work was funded by the National Institute of Environmental Health Sciences (U2CES030170). PNNL also supported this task. The team performed lipid measurements using mass spectrometry at the DOE Science Department’s user facility, EMSL, Institute for Molecular Science, PNNL.