A discovery by a Washington State University researcher may hold the key to preventing the severe, deadly pneumonia seen with COVID-19.
For more than a decade, Professor Santanu Bose, a viral infection researcher in WSU’s Department of Veterinary Microbiology and Pathology and his team, have worked to learn why some viral infections of the respiratory tract are so deadly.
Bose’s patented discovery involves a protein, A9, which signals an overblown inflammatory reaction in the airways that fills the lungs with fluid, destroys airway tissues, and results in fatalities.
“Patients often display a full spectrum of individual responses to respiratory infections, from mild to full-blown inflammatory storms,” Katrina Mealey said. Professor Mealey is the WSU veterinary college’s associate dean for research and a pharmacologist and veterinarian familiar with treating animals with respiratory infections. “A human therapeutic capable of calming the inflammatory storm in the lungs could be a game-changer,” she said.
Last week, Bose’s technology, patented as, “Methods of treating inflammation associated airway disease and viral infections,” was licensed to a Canadian Biotech company, InflammatorRx Inc., for further pre-clinical development intended as a precursor to human clinical trials with COVID-19 patients.
“Dr. Santanu Bose and his research team are on the trail of a remarkable find that may offer hope with the COVID-19 virus,” WSU veterinary college Dean Robert Mealey said.
What respiratory viruses do
“In a real sense, the inflammatory process goes into a sort of hyperdrive when it senses an infectious virus like SARS-CoV-2, the virus that causes COVID-19,” Bose said. “For some people, the inflammatory process goes beyond being beneficial to, in many cases, being fatal.”
Bose spent a large part of his professional life collaboratively researching the fundamental questions surrounding the body’s overblown inflammatory response.
“We started out wanting to know what happens when a virus first attacks the cells in our respiratory system. What reactive chemicals are produced that mount, and grossly amplify, this often-fatal inflammatory response associated with deadly pneumonia?”
“And secondly, we wanted to know if we could develop a treatment to interrupt the activity of any molecules that promote inflammation to moderate the response, so it still works enough to kill the virus and yet does not kill the patient at the same time,” Bose said.
It was Bose and colleagues’ work with an Influenza A virus (IAV) model in mice that led to the discovery of the A9 protein. A9, known formally as the S100A9 protein, is produced in large quantities almost immediately when a virus contacts the host cells it attacks.
“We soon learned the A9 protein plays a key role in promoting and overamplifying the inflammatory response. And that in turn leads to the resulting chemical cascade that causes severe pneumonia,” Bose said. “Our research group sought to partially block A9 with a neutralizing antibody to dampen but not completely block the inflammatory response.”
Bose turned to Professor Phillipe Tessier from Laval University in Quebec. Tessier possessed a neutralizing A9 antibody, including a humanized A9 antibody and agreed to help.
Antibodies are made by exploiting the body’s response to foreign proteins. When foreign proteins enter an animal or person’s bloodstream, the immune system reacts. The result among many is antibody production.
Antibodies are proteins also, but they are naturally specific and bind to the proteins which trigger their development. Typically, antibodies will destroy or eliminate foreign proteins from the body to prevent disease.
In this case though, the antibody made against A9, which is not a foreign protein, is designed to diminish the immune response, not destroy it.
The group published results as far back as 2014 in the peer-reviewed journal, PLoS Pathogens. That work demonstrated that the A9 neutralizing antibody did in fact dramatically reduce disease severity and deaths caused by an influenza A virus in a mouse model.
Subsequent research by other groups has shown that the A9 protein plays an amplifying role in other respiratory infections caused by other respiratory viruses, confirming the initial findings by Bose.
“Of particular relevance, a recent research work reported high levels of A9 protein in the lungs of critically ill COVID-19 infected patients,” Bose said.
“I believe our A9 technology could be utilized to combat COVID-19 for several reasons. RNA viruses like COVID-19 are prone to frequent mutations. Vaccines and anti-viral therapeutics which target the current virus strain, may not be effective against any evolved COVID-19 strains or other coronaviruses that may emerge in human populations in the future. It is the pneumonia due to massive airway inflammation that is associated with mortality of COVID-19 patients. We believe A9 technology can prevent that from happening.”
Another serious condition that occurs in cases of COVID-19, is the formation of unwanted blood clots. And while that is serious enough itself, once formed, blood clots can move throughout the body with devastating consequences.
Blocking A9 with the neutralizing antibody has been shown to reduce blood clots like those that are now being reported in patients with COVID-19 infections.
“A9 amplifies many aspects of the inflammatory response, including the migration of white blood cells to the lung, thrombosis and the deadly cytokine storm associated with COVID-19. This is what makes it such a promising drug target.” Philippe Tessier said.
WSU patents and licenses related to A9 technology
The WSU Office of Commercialization worked on Bose’s behalf to secure a patent in 2018 on the use of A9 technology to treat viral respiratory infections. InflammatorRx, the company that licensed this technology, intends to conduct pre-clinical and human clinical trials using Bose’s technology.
“We are very excited with this technology,” InflammatoRx CEO, Caroline Fortier said. “Our plan is to initiate toxicology studies before the end of the year on the humanized anti-A9 antibody.”
“This is a great example of WSU faculty research with potential for novel and effective treatments for the ongoing virus pandemic,” Sita Pappu, assistant vice president for commercialization at WSU said. “It is gratifying to support WSU research that might make a difference to public health.”
“Our goal now at WSU,” Bose explained, “is to immediately study the A9 antibody with the COVID-19 virus to ensure that neutralizing the A9 protein is effective in decreasing the inflammatory response and severity of the pneumonia, which should translate to increased overall patient survival.”
- Charlie Powell, public information officer, WSU College of Veterinary Medicine, 509‑595‑2017, firstname.lastname@example.org