The SARS-CoV-2 virus extensively hijacks the body’s fat processing system

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.

After discovering the important role of SARS-CoV-2 in fat, scientists sought to block the virus in cell culture using weight loss drugs and other fat-targeting compounds. When the fat fuel was shut off, the virus stopped replicating within 48 hours.

Author of recent papers Nature Communications Note that the result is in cell culture, not in humans. More research remains to see if such compounds are promising for people diagnosed with COVID. However, scientists at Oregon Health & Science University and the Pacific Northwest National Laboratory of the Ministry of Energy call this study an important step towards understanding the virus.

This is an exciting job, but it’s the beginning of a very long journey.We have some interesting observations, but there is much more to learn about the mechanism of this disease... “

Fikadu Tafesse, Research Author and Assistant Professor of Molecular Microbiology and Immunology, Oregon Health & Science University

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 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 have also been found to be important for the COVID virus.

“Lipids are an important part of every cell. Lipids literally connect us by keeping cells intact and are the main energy storage source for our body,” said PNNL’s biomedicine, which specializes in measurement. Scientist Jennifer Kyle says. Of lipids. “They are attractive targets for the virus.”

When we need energy, cells break down triglycerides into useful sources-; the three fatty acids contained in each triglyceride molecule.

The team discovered that SARS-CoV2 does not simply increase the number 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 24 of the 29 proteins of the virus on lipid levels. 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 disrupt the body’s fat processing system. Some have proven effective in preventing the virus from replicating in the laboratory.

Orlistat, a lipase inhibitor that is an approved weight-loss drug, 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 the virus replicates, it requires a continuous supply of energy,” said Tafes, who saw the changes in lipids as a result of the Zika virus and HIV. “More triglycerides may provide that energy in the form of fatty acids, but we do not know exactly how the virus will use these lipids in their favor.”

This study is the result of an ongoing link between OHSU and PNNL. Four years ago, these institutions began a collaboration now known as the Pacific Northwest Biomedical Innovation Joint Institute (PMedIC). In this collaboration, scientists and physicians will work together to combine basic science and clinical experience to investigate diseases and develop innovative therapies.

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