New Antivirals Block Progression of Flu Virus
Author: CENTRE DE RECHERCHE CLINIQUE ETIENNE - LE BEL DU CHUS
Researchers have discovered a new antiviral that targets the host rather than viruses which could prevent viruses from acquiring drug resistance.
Main DigestDr. Martin Richter (pharmacology), investigator with the Center de recherche clinique Etienne-Le Bel (CRCELB) at the Center hospitalier universitaire de Sherbrooke (CHUS) and professor in the Faculty of Medicine and Health Sciences of the Universite 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.
Influenza - A viral infection that attacks your respiratory system; your nose, throat and lungs. Influenza, commonly called the flu, is not the same as the stomach "flu" viruses that cause diarrhea and vomiting. Flu is a respiratory infection caused by a number of viruses. The viruses pass through the air and enter your body through your nose or mouth. Between 5% and 20% of people in the U.S. get the flu each year. The flu can be serious or even deadly for elderly people, newborn babies, and people with certain chronic illnesses. Most people with the flu recover on their own without medical care. People with mild cases of the flu should stay home and avoid contact with others, except to get medical care.
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 Eric 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.
The flu virus needs a key to enter a cell in order to spread within the respiratory system. This key, found on the virus's surface, is a protein referred to as hemagglutinin. In order for the key to work, it must be keyed properly so that the virus can enter the cell and replicate. The virus's genetic code doesn't provide the tools needed to shape the key, so the virus must use the host to do so. The virus therefore uses the host's enzymes to ensure its own replication. The enzymes act like a master locksmith that can key the virus's hemagglutinin and activate the entrance key. This lets the virus take control of the cell and allows its free replication, allowing the disease to propagate in the respiratory system.
As things stand, there are only two types of antivirals approved for treating the influenza virus (flu virus), including Tamiflu and Relenza, yet multiple strains of the flu virus are increasingly resistant to antivirals. Nearly all H3N2 strains are resistant to one of the two types of antivirals, so these medications are no longer recommended for treating influenza. In addition, several strains of H1N1 - all of which were circulating during the 2007-2008 flu season, were resistant to Tamiflu. Most strains derived from H1N1 virus - derived from the 2009 pandemic and still circulating today - remain susceptible but many cases of resistance have been detected.
As a result, Martin Richter's research opens the way to the development of new antivirals based on patent-pending technology.
The Societe de commercialization et de valorisation de l'Universite de Sherbrooke (SOCPRA) holds the intellectual-property rights to the results of this research, which is available for marketing partnerships.
Positioned at the cutting-edge of today's major health issues, the Center de Recherche Clinique Etienne- Le Bel (CRCELB) of the Center hospitalier universitaire de Sherbrooke (CHUS) stands out for its integrated approach in which fundamental, clinical, epidemiological, and evaluative research coalesce. More than 200 basic-science researchers and clinicians pool their knowledge and expertise with the shared objective of developing new knowledge to maintain health, prevent disease, and improve patient care. More than 900 people take part in advancing health sciences.
The Center hospitalier universitaire de Sherbrooke has two constituent institutions: the CHUS - Fleurimont Hospital and the CHUS - Hotel-Dieu. Its mission is fourfold: care, teaching, research, and assessment of health-care technologies and modes of intervention. The fourth largest hospital center in Quebec, the CHUS plays a triple role of local, regional, and supra-regional hospital. The CHUS stands out for its many cutting-edge specialties such as gamma-knife radiosurgery, positron emission tomography (PET), interventional angiography, and neuro-oncology. The CHUS hospital community comprises nearly 10,000 individuals (employees, physicians, researchers, students, trainees, and volunteers) with a single objective: serving life.
Center de recherche clinique Etienne- Le Bel , CHUS - www.crc.chus.qc.ca | Center hospitalier universitaire de Sherbrooke (CHUS) - www.chus.qc.ca
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