Reference number : GC-2017-Q3-00351, amendment number : , agreement type : G, recipient legal name : Labonté, Patrick (Institut national de la recherche scientifique), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Collaborative Research and Development Grants - Project, program name french : Subventions de recherche et développement coopérative - projet, program purpose english : Several polymers have been studied for their broad spectrum antiviral activity. These antiviral polymers such as polyvinyl alcohol sulfate (PVAS), sulfated polysaccharides (SPS) and polynapthalene sulfate (PNS) are believed to act primarily through inhibition of viral entry. Their antiviral activities were shown to correlate with their amphipathic character and to be length dependent and were shown to act by blocking virus-cell interaction or fusion. Recently, a new type of antiviral polymer, derived from modified nucleic acids and called nucleic acid polymers (NAPs), has also been shown to have potent, broad spectrum antiviral activity._x000D_
Although the antiviral activity of NAPs in most viruses is confined to blocking viral entry and or fusion, an additional post-entry antiviral effect has been observed specifically in the case of Hepatitis B Virus (HBV) infection. This post entry activity is of important therapeutic potential as it is correlated with the elimination of serum HBV surface antigen (HBsAg), a critical event always observed in patients achieving control of their infection after antiviral therapy is stopped. Due to their good safety profile, the anti-HBV activity of NAPs has been evaluated in three proof-of-concept phase II clinical trials in patients from Bangladesh and Moldova by Replicor Inc (Montréal, Canada). When used in conjunction with a conventional immunotherapy (pegylated-interferon-alpha2a), the serum level of HBsAg declined by several logs in all patients. Such reduction in HBsAg is rarely seen in patients treated with any of the currently approved therapies for HBV infection. Due to the chronic nature of the HBV infection, the post-entry antiviral effect of NAPs is thought to be responsible for the profound reduction in HBsAg observed in treated patients. Therefore a better mechanistic understanding of the post-entry anti-HBV effects of NAPs would be beneficial to uncover the molecular machinery involved in these effects as they promise to reveal previously unknown biology in the replication cycle of HBV. Here I present a strategy for the investigation of the mechanism of action of NAPs in vitro in HBV expressing cells. _x000D_
_x000D_, program purpose french : Several polymers have been studied for their broad spectrum antiviral activity. These antiviral polymers such as polyvinyl alcohol sulfate (PVAS), sulfated polysaccharides (SPS) and polynapthalene sulfate (PNS) are believed to act primarily through inhibition of viral entry. Their antiviral activities were shown to correlate with their amphipathic character and to be length dependent and were shown to act by blocking virus-cell interaction or fusion. Recently, a new type of antiviral polymer, derived from modified nucleic acids and called nucleic acid polymers (NAPs), has also been shown to have potent, broad spectrum antiviral activity._x000D_
Although the antiviral activity of NAPs in most viruses is confined to blocking viral entry and or fusion, an additional post-entry antiviral effect has been observed specifically in the case of Hepatitis B Virus (HBV) infection. This post entry activity is of important therapeutic potential as it is correlated with the elimination of serum HBV surface antigen (HBsAg), a critical event always observed in patients achieving control of their infection after antiviral therapy is stopped. Due to their good safety profile, the anti-HBV activity of NAPs has been evaluated in three proof-of-concept phase II clinical trials in patients from Bangladesh and Moldova by Replicor Inc (Montréal, Canada). When used in conjunction with a conventional immunotherapy (pegylated-interferon-alpha2a), the serum level of HBsAg declined by several logs in all patients. Such reduction in HBsAg is rarely seen in patients treated with any of the currently approved therapies for HBV infection. Due to the chronic nature of the HBV infection, the post-entry antiviral effect of NAPs is thought to be responsible for the profound reduction in HBsAg observed in treated patients. Therefore a better mechanistic understanding of the post-entry anti-HBV effects of NAPs would be beneficial to uncover the molecular machinery involved in these effects as they promise to reveal previously unknown biology in the replication cycle of HBV. Here I present a strategy for the investigation of the mechanism of action of NAPs in vitro in HBV expressing cells. _x000D_
_x000D_, agreement title english : Characterization of the post-entry anti-HBV properties of nucleic acid polymers, agreement title french : Characterization of the post-entry anti-HBV properties of nucleic acid polymers, agreement number : CRDPJ, agreement value : 146921.0, agreement start date : 2017-10-18, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year (2017-2018 to 2019-2020)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2019-2020)., owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada