Day 1 :
Keynote Forum
Khaled Barakat
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
Biography:
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.
Abstract:
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.
Keynote Forum
Yolanda Revilla
Centro de BiologÃa Molecular “Severo Ochoaâ€, Spain
Keynote: Monocyte Porcine Cell lines for Productive African Swine Fever Virus Infection
Time : 10:00-10:30
Biography:
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).
Abstract:
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.
Keynote Forum
Hiroshi Ohrui
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
Biography:
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.
Abstract:
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 polymerasesâ€. 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.
- Host Immune Defences & Immunotherapy
Viral hepatitis
Veterinary Virology
Viral Evolution & General Virology
HIV & Other Emerging Viruses affecting Afro-Asian Continents
Location: Madrid, Spain
Chair
Khaled Baraket
University of Alberta, Canada
Co-Chair
Angelika Krumina
Riga Stradins University, Latvia
Session Introduction
Shen Kunling
Capital Medical University, China
Title: Inhaled IFN-α1b for RSV bronchiolitis
Time : 11:30-12:30 Workshop
Biography:
Shen Kunling is the Professor, Doctoral Supervisor and Physician Director. She has studied as a Visiting Scholar in Switzerland Infectious Disease Control Center, Australia Sydney Alexander Children's Hospital and Medical College of Wisconsin. She has been serving as the current Chinese Medical Association Pediatrics Chairman, Committee Member of the International Academy of Pediatrics, Committee Member of the Asian Academy of Pediatrics, Vice President of Pediatricians Branch of the Chinese Medical Association, Leader of Chinese Medical Association breathing professional team, Committee Member of the tenth Pharmacopoeia and Committee Member of Chinese Medical Association breathing surgeon branch.
Abstract:
Respiratory syncytial virus (RSV) is the most common pathogeny of bronchiolitis and 90% children are infected with RSV in their first 2 years. Interferon-α1b is the main subtype of alpha interferon in Chinese and has been widely used in viral disease treatment. A series of preclinical and clinical studies were carried out to evaluate efficacy and safety of IFN-α1b against RSV by aerosol inhalation. Animal PK and tissue distribution study demonstrates that after administration via aerosol inhalation, large amount of 125I-IFN-α1b concentrates in airway and stays longer than intramuscular injection. In a PD study, RSV infected mice which receiving inhaled IFN-α1b treatment show less tissue damage and lower RSV load in lung and increased CD3+CD8+ lymphocyte level in peripheral blood compared with control group. Both anti-RSV and immunoregulation effects of IFN-α1b are in a dose-effect manner. In a multicenter RCT study recruiting 330 acute bronchiolitis children, the total improvement rates of nebulized IFN-α1b 2 μg/kg and 4 μg/kg were 92.3% and 95.0% respectively and significantly higher than control group (85.3%, P<0.05). The effect on symptoms improvement of higher dose group is better than lower dose. The efficacy of IFN-α1b is better when used in early stage of disease and for RSV positive children. Irritation symptoms and serious adverse reactions were not observed. In summary, inhaled IFN-α1b is effective and safe for anti-RSV bronchiolitis in children.
Keivan Zandi
University of Malaya, Malaysia
Title: Selected bioflavonoids and their activity against Chikungunya virus in vitro replication
Time : 12:20-12:55
Biography:
Keivan Zandi has completed his PhD in Medical Virology from Tarbiat Modarres University, Iran. He is currently working as an Associate Professor in Department of Medical Microbiology, University Malaya. He has published more than 60 research papers in various scientific journals and has several Patents to his credit. He is actively severing as an Editorial Board Member for Scientific Reports with Nature publishing group as well as several other journals such as International Journal of Virology, SM tropical Medicine Journal, International Journal of Pharmacology, American journal of Drug Discovery and development and International Journal of Drug Discovery and Biotechnology journal.
Abstract:
The mosquito-borne Chikungunya virus (CHIKV) causes Chikungunya fever with clinical presentations such as severe back and small joint pain and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for Chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: Silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and a clinical isolate of CHIKV of the Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of the compounds was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, E1 proteins. Silymarin exhibited significant antiviral activity against CHIKV reducing both replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.
Jelena Prpic
Croatian Veterinary Institute, Croatia
Title: Detection and molecular characterization of hepatitis E virus in humans, swine and wild boars in Croatia
Time : 12:55-13:20
Biography:
Jelena Prpic has completed her PhD from University of Zagreb, Faculty of Science. She is a Senior Assistant at Department of Virology, Laboratory for Classical Swine Fever, Molecular Virology and Genetics at Croatian Veterinary Institute, Zagreb. She has published more than 21 papers in reputed journals.
Abstract:
Hepatitis E is caused by a RNA virus mostly transmitted by the fecal-oral route and is the cause of sporadic and epidemic forms of acute hepatitis. The causative agent of hepatitis E is a member of the Hepeviridae family, consisting two genera, Orthohepevirus (A, B, C and D) and Piscihepevirus. Members of species Orthohepevirus A is divided into four genotypes; HEV-1 and HEV-2 are human specific while HEV-3 and HEV-4 are known to have zoonotic potential. Because of the possibility of zoonotic transmission by contact with infected animals or through environmental exposure Hepatitis E is an important public health problem. A comprehensive survey based on viral RNA detection was carried out in Croatia including IgM positive human sera samples and blood, tissue and feces samples originating from swine and wild boars. Molecular characterization of ORF1 genomic region confirmed the phylogenetic clustering of the obtained sequences into genotype 3, previously reported in Europe. Furthermore, our results proved the presence of identical sequence variants in different samples, regardless of their origin, age or habitat of the host, suggesting mutual source of infection or interspecies transmission. Moreover, a close genetic relationship of Croatian animal strains and known human HEV strains from the GenBank opens the question of possible cross species HEV transmission in Croatia.
Ahmed Al-Qahtani
King Faisal Specialist Hospital and Research Center, KSA
Title: Specific mutations in the X gene of hepatitis B virus: Characterization and impact on disease progression in HBV infected Saudi patients
Time : 14:05-14:30
Biography:
Ahmed Al-Qahtani has completed his PhD in Cellular Biology from the University of Georgia, USA in 1996. He is the currently a Senior Scientist and Head of the Molecular Virology Section at the Research Center of King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia. He is a Professor of Microbiology and Immunology at the College of Medicine of Alfaisal University in Riyadh, Saudi Arabia and an Adjunct Associate Professor at College of Medicine of King Saud University in Riyadh, Saudi Arabia. He has published nearly 60 papers in reputed journals in the field of molecular and cellular biology of infectious organisms and serves as a Reviewer for several scientific journals.
Abstract:
Objectives: Hepatitis B virus (HBV) is one of the most widespread human pathogens causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). This study investigated the clinical impact of single and combination mutations in the HBx gene on the pathogenesis of HCC through progressive stages of liver disease and also assessed HBV genotypic variation within the Saudi population. Methods: Four hundred and twenty four Saudi patients infected with HBV were enrolled in this study. The patients were categorized into inactive HBV carriers (IC), Active HBV carriers (AC), liver cirrhosis (LC) and HCC groups based on disease severity. All the samples were analyzed for mutations in HBx using PCR and direct sequencing. Results: Male sex, age>50 years and high serum ALT level were found to be associated with risk of progressive liver disease. HBV genotype D was the predominant genotype present among the study group (93%) with sub genotype D1 being the most abundant (62.5%). 78.5% HCC patients were infected with HBV sub genotype D1. Liver cirrhosis was predominantly present in patients with HBV genotype C (66.7%). Mutations I127T, V131I and F132Y/I/R showed a significantly increasing trend with disease progression to HCC. Mutation V88F was present in all the HCC patients. H94Y and K130M were also significantly associated with severe liver disease. One double mutation (K130M+V131I) and two triple mutations (I127T+K130M+V131L and K130M+V131I+F132Y) were observed with significant rising prevalence through progressive clinical phases of liver disease to HCC. Conclusion: Several single and combinational mutations in the HBx, correlating with severity and progressive clinical phases of HBV infection were identified. The mutational combinations may have a synergistic effect in accelerating progression to HCC. These specific patterns of HBx mutations can prove useful in predicting the clinical outcome of HBV infected patients and may serve as early markers of high risk of developing HCC in the Saudi population.
Sharad Yadav
DUVASU, India
Title: Bovine Herpes Virus-1 (BHV-1): Current scenario of South and East Asia
Time : 14:30-14:55
Biography:
Sharad Kumar Yadav has 25 years of teaching and research experience and has served to various senior positions of the University including Registrar of the DUVASU University. He is currently a Professor and Head of the Department of Veterinary Microbiology, at DUVASU, Mathura, India. He has published number of papers in reputed international & national journals and has a vast experience in the arena of BHV-I virus.
Abstract:
Bovine herpesvirus-1 (BoHV-1) is accountable for infectious bovine rhinotracheitis (IBR), a disease of major economic thrashing in the cattle industry globally. BHV-1 is a member of the genus Varicellovirus in the sub family Alphaherpesvirinae, belonging to the family Herpesviridae. The property of establishing a latent state in ganglionic neurons after infection allocates the BHV-1 virus to persist in the body and spread the disease from a latently infected carrier to a non-infected herd. The first report of BHV-1 infection was recorded as genital form of disease as infectious pustular vulvovaginitis (IPV) in cattle in 1841 in Germany. Viral association with this form of disease was confirmed in 1928; respiratory form (IBR) was observed in 1950s and in 1958 for the first time the virus was isolated successfully and classified in the family Herpesviridae. BHV-1 is currently widespread all over the world and observed in USA, Canada, Zaire, Italy, Belgium, India, Japan, Taiwan and Turkey. The documented prevalence of BHV-1 is 83% in UK, 63-86% in Egypt, 43% in England, 36-48% in Central and South America, 36% in China, 14-60% in Africa and as restricted distribution in India. Among East and South Asian countries in Nepal, Sri Lanka, Korea, Bhutan and Bangladesh disease was not reported. BHV-1 virus has been detected in many states of India like Uttar Pradesh, Uttarakhand, Haryana, Kerala, Punjab, Chhattisgarh, Gujarat, Maharashtra, Tamil Nadu, Orissa, Arunachal Pradesh, Nagaland and Karnataka with maximum prevalence in Uttar Pradesh and minimum in Himachal Pradesh. Considering the emerging nature of virus, latency, unusual rate of spread of the infection with economic aspects, the current scenario of BHV-1 in South and East Asian region is addressed to formulate a comprehensive control strategy involving thorough screening before international trading and restricting animal movements between different parts of world.
Jayaraman Shanmugam
Sri Balaji Vidyapeeth, India
Title: Arboviral infections in India and south East Asian countries
Time : 14:40-15:05
Biography:
Jayaraman Shanmugam is the President of Indian Association of Medical Microbiologists (2014-2015) and has worked at Sri Chitra Tirunal Institute for Medical Sciences and Technology (Government of India), Trivandrum for 26 years and later in two private medical colleges for 14 years in UAE and India. He has completed 24 research projects, published 118 papers in various journals, received 18 awards and many honors, edited two journals, organized many workshops, symposia, CME, national and international conferences, guided PhD students and he is an elected fellow of five societies including American College of Epidemiology and a Senior Consultant in Medical Virology/Microbiology in India.
Abstract:
More than 40 human viral agents have emerged in various parts of the world during the past four decades. Most of them are RNA viruses mainly transmitted from animals to humans. Maximum viruses have emerged in the African, Asian and South American continents where enormous species of animals, birds and insects are living with increased possibility of humans coming in close contact with them directly or indirectly. Though more than 550 types of arboviruses have been described in the world, only around 15 types of them have been reported in India. The Kyasanur Forest Virus in India emerged in 1957 in Karnataka state. In 2005-2006 a major Chikungunya outbreak occurred in South India. The arbovirus emerged lately in India is Congo-Crimean Hemorrhagic Fever virus in 2012 in Gujarat. Around 10 new types of viruses have been detected in South East Asia and Western Pacific. In Australia nearly 40 arboviruses have been described. Due to the paucity of laboratory facilities many viral diseases go undiagnosed in developing countries from Africa and Asia. Hence the health authorities should initiate appropriate measures to establish high quality laboratories to diagnose viral diseases without delay, including periodic training of the laboratory personnel.
Pedro Brandao dos Santos Pedrosa
Leibniz Universität, Germany
Title: Biosafety in the research and clinical practice dealing with emerging viral pathogens especially in the scenario of an outbreak and respective to the point of evolution of virulence as a biosafety factor
Time : 15:20-15:45
Biography:
Pedro Brandao dos Santos Pedrosa has obtained his BSc in Microbiology and Immunology. He is Specialist in Biosafety by FIOCRUZ (IPEC) and completed his MSc in Immunology from USP (São Paulo State University). His virology experience comprises work with Dengue virus, Hantavirus, Mayaro virus, some degree of training in BSL3 operation, training and scientific initial work in the Friedrich Loeffler Institute (FLI-INNT). He has 1 article published to his credit.
Abstract:
The previous theory of the epidemiological transition has been challenged this time by the worst EHF epidemic ever (caused by EBOV), which may pose a real threat of pandemic through the return of unresolved cases to their countries of origin. This instance exemplifies which sort of consequences the virological research community is about to deal with in the case of research of emerging/reemerging viral pathogens presenting a relevant process of evolution of virulence. The process of evolution of virulence of viral pathogens of medical importance can no longer be regarded with outdated paradigms and dogmatic or misconceived views concerning fast evolving viruses presenting an actual and significant evolution of virulence such as DENV and some coronaviruses (i.e., SARS-CoV and MERS-CoV). The lecture will present the evolution of virulence of such viral pathogens as a relevant factor concerning the biosafety of the virological research.
Francois Dufrasne
Universite Catholique de Louvain, Belgium
Title: Single amino acid substitution in the HIV-2 gp36 ectodomain part interacting with BST-2 impairs viral release
Time : 15:45-16:10
Biography:
Francois Dufrasne is an Assistant Doctorate at AIDS Reference Laboratory, Universite catholique de Louvain. He is a Member of several scientific societies like Belgian Society of Pharmaceutical Sciences, Society of Medicinal Chemistry in France, Member of the American Chemical Society, Member of scientific committees and organization: Eleventh Franco-Belgian Days Pharmacochemistry, Member of the Permanent Organizing Committee for Franco-Belgian days Pharmacochemistry, Committee Member Reading of Tetrahedron Letters, Member of the reading committee of journals Tetrahedron, Tetrahedron Letters, European Journal of Medicinal Chemistry, Synthesis.
Abstract: