Dis­cov­ery of New An­tivi­rals That Block the Pro­gres­sion of the Flu Virus

Stanstead Journal - - FROM PAGE 1 - Sher­brooke

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.

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 So­ciété de com­mer­cial­i­sa­tion et de val­ori­sa­tion de l’Univer­sité de Sher­brooke (SOCPRA) holds the in­tel­lec­tual-prop­erty rights to the re­sults of this re­search, which is avail­able for mar­ket­ing part­ner­ships.

Cen­tre de recherche clin­ique Éti­enne-Le Bel, CHUS ::: www.crc.chus.qc.ca

Po­si­tioned at the cut­ting-edge of to­day’s ma­jor health is­sues, the Cen­tre de Recherche Clin­ique Éti­enne-Le Bel (CRCELB) of the Cen­tre 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.

Cen­tre hos­pi­tal­ier univer­si­taire de Sher­brooke (CHUS) ::: www.chus.qc.ca

The Cen­tre hos­pi­tal­ier univer­si­taire de Sher­brooke has two con­stituent in­sti­tu­tions: the CHUS – Fleu­ri­mont Hospi­tal and the CHUS – Hô­tel-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 suprare­gional 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.

Photo courtesy

Dr. Martin Richter

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