Day 1 :
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
Keynote: Toward Potent Immunotherapy Drugs: Rational Design of Inhibitors of the Immune Checkpoints Proteins
Time : 09:30-10:00
Dr. Barakat is an Assistant Professor at the school of Pharmacy at the University of Alberta, Canada. His research stands at the multidisciplinary interface of physics, biology and computer science. Barakat’s major focus is on developing and applying state-of-the-art computational drug discovery tools to discover new antiviral and immunotherapeutic drugs. Barakat has made great contributions in understanding the nature and biophysical processes underlying protein–drug, protein–protein and drug off-target interactions and predicting drug-mediated toxicity. He also received numerous awards including the CIHR and AIHS postdoctoral fellowships, the prestigious University of Alberta dissertation award and many distinction awards throughout his undergraduate and graduate studies. Dr. Barakat is also the editor of the Journal of Pharmaceutical Care & Health Systems and serves as a guest reviewer for several journals.
Immune checkpoints constitute a distinctive set of proteins that belong to the B7 family. The engagement of these transmembrane receptors with their ligands provides critical signals to inhibit T-cell activation and promote for immune tolerance. Tumor and infected cells can hide from the immune system by overexpressing these proteins leading to T-cell exhaustion. Blocking these interactions emerged as a ’game changing’ approach in anticancer and antiviral immunotherapy. Current immune checkpoints blockers are limited to antibodies and possess a unique mode of action; they reactivate exhausted T cells, allowing them to proliferate and recognize and kill infected and tumor cells. Despite their outstanding success the ultimate therapeutic target or combination of targets from these proteins is still to be determined. They are highly limited by their substantial cost and severe side effects. Our team at the University of Alberta has been focused on developing less expensive and more controlled inhibitors for the immune checkpoints. Our approach combines state-of-the-art computational modeling techniques with cutting-edge experimental technologies to design and develop small molecule inhibitors for these proteins. During this talk, an overview about our program will be presented with updates on our recent progress toward this goal.
Centro de Biología Molecular “Severo Ochoa”, Spain
Time : 10:00-10:30
Yolanda Revilla is the Doctor of Biological Sciences, field of Biochemistry and Molecular Biology from the UAM in 1985. She is currently a Researcher and Head of Lab in the CBMSO-CSIC-UAM, where she leads a group of 7 people including 3 students of master thesis, 3 postdoctoral and a technician. She is a Member of Scientific Boards of ASFORCE, Evaluation Committees Curie/EU Commission and ASFV Global Research Association (GARA).
ASFV is highly pathogenic double-stranded DNA virus with a marked tropism for cells of the monocyte-macrophage lineage. Although monkey cell lines such as Vero or COS allow the adaptation of ASFV strains after several passages, a suitable porcine cell line able to efficiently support ASFV infection is necessary to develop models for cell-host interaction and vaccine studies. For this purpose, four different porcine cell lines from monocyte-macrophage origin (IPAM WT, IPAM-CD163, CΔ2+ and WSL) have been tested in order to set up the most similar conditions to the infection in primary alveolar macrophages (PAM) in terms of phenotype, ASFV infection susceptibility and viral production. To achieve this, we analyzed on these lines the presence of CD163 and CD169 cellular surface receptors since they are linked to differentiation and maturation of the macrophages and seem to be closely related to ASFV infection. ASFV susceptibility was analyzed in the infected cells by the expression of the viral late protein p72 and viral production by titration on plaque assays. Results showed that although all porcine cell lines analyzed were susceptible to ASFV infection, none of them was as efficient as PAM in terms of virus production. Future experiments will be focus on describing which cellular factors are related with the ability of porcine cell lines to support an ASFV productive infection in order to establish a suitable model of study.
Yokohama University of Pharmacy, Japan
Keynote: Design and Synthesis of Anti-Viral Modified Nucleosides Based on a New Concept to Win the Battle Against Emerging Viruses
Time : 10:30-11:00
Hiroshi Ohrui has received his PhD degree (1971) from The University of Tokyo. He has joined RIKEN (1966), moved to Tohoku University (1881) and then to Yokohama University of Pharmacy (2006). He has worked for Dr. J. J. Fox at Sloan Kettering Institute for Cancer Research (1972), for Dr. J. G. Moffatt at Syntex Research (1973) and for The Technical University of Darmstadt (1990). His research interests cover organic synthesis, chemical biology, and chiral discrimination.
Many emerging viral infectious diseases, for example, the spreads of AIDS, Flu, West Nile Viruses, SARS, Ebola, and so on, are causing major threats to global public health. Viruses adapt themselves to the environmental change by mutation. Mutation causes the emergence of mutants resistant to drugs and or vaccines. Therefore, it has been thought that the treatment of viral infectious diseases is very difficult due to the emergence of resistant mutants. However, I would like to propose a new concept that mutation is the heaven-sent opportunity for the development of anti-viral modified nucleosides for the following reasons. “Mutation is that viruses change their genes by taking incorrect (not programmed) nucleosides into them. This indicates that the substrate selectivity of viral nucleic acid polymerases is not strict. On the other hand, human beings do not change their genes by taking incorrect nucleosides. This indicates that the substrate selectivity of human nucleoside polymerases is very strict. Thus, by taking advantage of the different substrate selectivity, it will be possible to develop anti-viral modified nucleosides which are selectively incorporated into viral nucleic acids and inhibit their nucleic acid polymerases”. We have been working on the development of anti-viral modified nucleosides based on the concept. The development of EFdA (prevents the emergence of resistant mutants, is supremely high anti-HIV active and low toxic) and CycloSal-EdA [active against Flu-virus, Japanese encephalitis virus (JEV) and Ebola] will be presented. The development of the facile synthetic method of these modified nucleosides will be also discussed.