Targeting signaling cascades for antiviral therapy against Influenza infection
Advisor Information
Tomas Helikar
Location
Milo Bail Student Center Ballroom
Presentation Type
Poster
Start Date
8-3-2013 1:00 PM
End Date
8-3-2013 4:00 PM
Abstract
Among emerging infectious diseases, high morbidity and mortality attributed to influenza make it a major threat to human populations worldwide. Immunoprophylactics and antiviral drugs are limited in prevention and treatment, due to selective pressure and increasing resistance among circulating strains, necessitating the need to develop novel therapeutics for the control of an influenza outbreak. However, identification of drug targets has been challenging since the replication of the influenza virus is governed by an intricate network of intracellular regulatory events in addition to an even more complex system of biochemical interactions of the host cell. In this study, we present the first large-scale dynamical model of the molecular mechanism of influenza infection. Each step of the viral life cycle from endocytosis to the budding of progeny virions has been modeled in addition to cellular pathways that are evoked and exploited by the cell obligate parasite. Simulations and analyses of the models dynamics qualitatively reproduced numerous biological phenomena discovered in the laboratory. Finally, the model has been used to compare current and proposed drugs against influenza. Our results indicate that targeting a specific binding interface in the viral proteins is more efficient in reducing replication than existing use of Amantadine/Rimantadine or Zanamivir/Oseltamivir. This study provides a better understanding of molecular dynamics of and interactions between viral proteins and host proteins, which is expected to improve vaccine strain selection and novel drug development to prepare us for the next inevitable outbreak.
Targeting signaling cascades for antiviral therapy against Influenza infection
Milo Bail Student Center Ballroom
Among emerging infectious diseases, high morbidity and mortality attributed to influenza make it a major threat to human populations worldwide. Immunoprophylactics and antiviral drugs are limited in prevention and treatment, due to selective pressure and increasing resistance among circulating strains, necessitating the need to develop novel therapeutics for the control of an influenza outbreak. However, identification of drug targets has been challenging since the replication of the influenza virus is governed by an intricate network of intracellular regulatory events in addition to an even more complex system of biochemical interactions of the host cell. In this study, we present the first large-scale dynamical model of the molecular mechanism of influenza infection. Each step of the viral life cycle from endocytosis to the budding of progeny virions has been modeled in addition to cellular pathways that are evoked and exploited by the cell obligate parasite. Simulations and analyses of the models dynamics qualitatively reproduced numerous biological phenomena discovered in the laboratory. Finally, the model has been used to compare current and proposed drugs against influenza. Our results indicate that targeting a specific binding interface in the viral proteins is more efficient in reducing replication than existing use of Amantadine/Rimantadine or Zanamivir/Oseltamivir. This study provides a better understanding of molecular dynamics of and interactions between viral proteins and host proteins, which is expected to improve vaccine strain selection and novel drug development to prepare us for the next inevitable outbreak.