Researchers identify new function for matriptase enzyme

Published on February 24, 2013 at 4:49 AM · No Comments

Dr. Martin Richter (pharmacology), investigator with the Centre de recherche clinique Étienne-Le Bel (CRCELB) at the Centre hospitalier universitaire de Sherbrooke (CHUS) and professor in the Faculty of Medicine and Health Sciences of the Université de Sherbrooke (UdeS), and his collaborators have identified a new function of the enzyme matriptase, present in the human respiratory system, that can activate a viral protein involved in infections caused by the H1N1 influenza (or flu) virus. Using this observation as a starting point, these researchers have discovered a new antiviral that targets the host rather than viruses, which could prevent viruses from acquiring drug resistance. Martin Richter's research findings provide a response to a critical need for new antivirals to treat the flu, which, even today, annually causes between 250,000 and 500,000 deaths across the world, especially among young children and the elderly.

Martin Richter and his coworkers at CRCELB and the Institut de pharmacologie de Sherbrooke (pharmacology institute), namely medical chemist Éric Marsault and biochemist/pharmacologist Richard Leduc, have developed molecules capable of blocking this enzyme's activity, which impairs the virus's propagation. The research team has filed an international patent application for a new class of influenza antivirals targeting matriptase and recently published its research findings in the renowned Journal of Virology.

Martin Richter's results demonstrate that biotechnology tools referred to as interfering RNA can be used to suppress matriptase expression in human bronchial epithelial cells. These cells cover the body's respiratory tract and are the main target of the flu virus. The team of researchers was therefore able to demonstrate that the enzyme's absence significantly blocked replication of the H1N1 virus. Without this enzyme present, these respiratory cells offer greater resistance to the flu virus. The researchers took their work a step further by using their novel inhibitor to suppress the enzyme's action. Indeed, they demonstrated that the inhibitor was highly effective in blocking replication of the H1N1 virus, which caused the 2009 pandemic.

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