Using newly developed mouse models of acute lung damage, the researchers found that exposure to SARS-CoV-2 spike protein alone was enough to induce symptoms similar to COVID-19, including severe inflammation of the lungs. SARS-CoV-2 is the virus that causes COVID-19, which is covered with tiny spike proteins. These proteins bind to receptors on our cells, initiating a process in which the virus releases its genetic material into healthy cells.
Using newly developed mouse models, the researchers found that exposure to SARS-CoV-2 spike protein alone was enough to induce symptoms similar to COVID-19, including severe inflammation of the lungs. The lung tissue of healthy mice is pictured on the left and the lung tissue of mice exposed to spike proteins on the right.
Source: Pavel Soropov, Old Dominion University
“Our results suggest that even without a complete virus, SARS-CoV2 spike protein can cause lung damage,” said Dr. Pavel Solopov, an assistant professor of research at Frank Reidy Center for Bioelectronics at Old Dominion University. “This previously unknown mechanism can cause symptoms before a large number of virus replication occurs.”
Soropov presented the new study April 27-30 at the 2021 meeting of the Virtual Experimental Biology (EB) annual meeting of the American Society of Pharmacology and Experimental Therapy.
Studying SARS-CoV-2 can be challenging because experiments involving complete viruses require a Biosafety Level 3 laboratory. To overcome this obstacle, the researchers created a new model of acute lung damage that uses genetically modified mice to express SARS-CoV-2 human receptors in their lungs.
“Our mouse model greatly reduces the risk of doing this type of research by allowing COVID-19 lung damage to be studied without the use of complete live viruses,” Soropov said. “This will increase and enrich the ability to conduct COVID-19 research. Our model may also be useful for studying other coronaviruses. ”
The researchers injected genetically modified mice with a spiked protein and analyzed their responses after 72 hours. The other group of mice received only physiological saline as a control.
The researchers found that genetically modified mice injected with spike protein exhibited COVID-19-like symptoms, including severe inflammation, white blood cells pouring into the lungs, and evidence of cytokine storms, an immune response in which the body begins to attack its cells and tissues, not just against the virus. Mice that received only physiological saline remained normal.
“These findings suggest that genetically modified mice, along with only one spike protein, could be used to study SARS-CoV-2 lung damage,” Soropov said. “We can use this tool to better understand how to spike proteins cause lung symptoms, even in the absence of a complete virus, so that we can use this to develop new targets and drugs to treat COVID-19.”
The researchers plan to continue this research route, using new mouse models to study the effectiveness of several drugs in reducing acute lung damage and the severity of COVID-19.
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