Innovative Approaches for Antiviral Agents

GRACIELA ANDREI holds a PhD in Biological Sciences and is an Assistant Professor at the Faculty of Medicine, Katholieke Universiteit Leuven, Belgium. At the Rega Institute for Medical Research, Department of Microbiology and Immunology, she carries out her research work that is mainly focused on chemotherapy of viral diseases, with emphasis on herpesviruses (cytomegalovirus, varicella-zoster virus and herpes simplex), poxviruses (vaccinia, cowpox, orf), polyomaviruses and papillomaviruses, and the study of the molecular mechanisms underlying the antiviral drug resistance phenomenon and anticancer activity of nucleotide analogues. Dr. G. Andrei has authored approximately 30 and co-authored approximately 260 papers in international peer-reviewed journals between 1983 and 2011. She has also (co)authored 6 book chapters and 10 proceedings articles and about 260 published abstracts between 1983 and 2011.

DANIEL APPELLA was graduated from the University of Wisconsin-Madison, 1998, with Ph.D. in Organic Chemistry. He continued with a postdoc at MIT, also working in the area of organic chemistry. He was an assistant professor at Northwestern University, in the Chemistry  Department, from 2001 to 2004. In 2005 he moved to NIH as a tenure track PI, promoted to tenure at NIH in 2008. Currently, he is Chief of the Synthetic Bioactive Molecules Section, one of the labs in the Laboratory of Bioorganic Chemistry that is part of the National Institute of Diabetes and Digestion and Kidney Diseases (NIDDK). Appella’s laboratory research uses synthetic organic chemistry to create new molecules with unique biological activity with the potential to evolve into a new strategy for diagnosing or treating a disease. Within their research, most of the time goes for the molecules synthesis, and the use of a large amount of molecular modeling and biophysical techniques to study the molecules they make. Different projects of the Appella’s group are: A) exploration of the incorporation of carbocyclic rings and sidechains into the backbone of several different peptide nucleic acids (PNAs) in order to provide the basis for design of PNA-based sensors and to develop new diagnostic techniques based on our modified PNAs; B) examination of sidechain-bearing polyamines as molecular scaffolds for the display of RNA binding groups, in order to develop syntheses of these polyamines, making combinatorial libraries of these molecules, and studying their binding properties to two important RNA targets (TAR RNA and RRE RNA of HIV); C) inspired by a recent identification of a few novel molecules that reactivate mutant p53 to bind its DNA target, the 3rd research topic is to design a new class of molecules that reactivate mutant p53 in order to probe the unique mechanism that allows small organic molecules to restore normal activity to a mutant protein.

MAURIZIO BOTTA graduated with honors in chemistry at the University of Rome in 1974. After his military service he returned to work at the Institute of Organic Chemistry, University of Rome with the title of Fellow , under the guidance of Prof. R. Nicoletti . In 1977 he started at the University of New Brunswick (Canada) , a period of research under the guidance of Prof. K. Wiesner , earning his PhD in November 1979 . Since December 1979 resumed scientific and educational cooperation with Prof. R. Nicoletti at the University of Rome becoming a researcher . Winner of a bag NATO in 1985, he traveled for a year in laboratories of Prof. S. Hanessian of the ‘ University of Montreal (Canada) , as invited researcher .In October 1987 as an Associate Professor of Pharmaceutical Chemistry , he has held the chair of Analysis Pharmaceutical Chemistry III of the Degree Course in Pharmaceutical Chemistry and Technology of Faculty of Pharmacy, University of Siena and Bioorganic Chemistry for substitution at the Faculty of Mathematical, Physical and Natural Sciences. In the periods July-September 1987 – July September 1988 and from November to January 1989 he was Invited Professor at the University of Montreal (Canada). Since 2000 he is Full Professor of Pharmaceutical Chemistry at the University of Siena and holds the task of teaching Complements of Medicinal Chemistry and Synthesis and Design of Drugs for the Master of Science in Pharmaceutical Chemistry , University of Siena. In years 2002-2008 he held the position of Director of the Department of Drug Chemistry and Technology University of Siena. Prof. Botta was a member of the Board of the Division of Pharmaceutical Chemistry Society Italian Chemical from 1998 to 2004 , Director of the School ‘s annual ” Laboratory Methods Synthetic Medicinal Chemistry ” organizer of the workshop ” European Workshop on Drug  Design ” , now in its seventh edition and ‘ ” European Workshop in Drug Synthesis ” , at the University of Siena and he  is also a member of ‘ editorial board of scientific journals such as ” ChemMedChem ” , “Current Pharmaceutical Design” and ” Journal of Medicinal Chemistry ” . Since January 2008 he is Adjunct Professor at Temple University ‘s College of Science and Technology in Philadelphia (USA). The research group of Prof. Botta, currently consists of about 30 young people between undergraduates , graduate students,research grant and a single researcher , is active in the synthesis and structure determination of biologically active natural products , organic synthesis and testing of potential agents anti-viral and anti-cancer , anti-tuberculosis and synthesis of antifungal compounds . The techniques used to these studies can be summarized in conventional techniques for organic synthesis , synthesis techniques for small molecules in the solid phase , the use of enzymes , microwaves , and parallel synthesis, also  molecular modeling techniques , such as docking , molecular dynamics , QSAR and 3D QSAR Virtual screening , generation of virtual libraries are used for the discovery and optimization of potential drugs . Recently, next to the chemical synthesis and Computational has also added the analytical chemistry for the determination of parameters Pharmacokinetic necessary for the optimization of pharmacologically active molecules . The scientific production of Professor Botta is summed up in about 460 publications in journals International , 15 patents and more than 150 conference papers .

ANDREA BRANCALE is a Professor in Medicinal Chemistry at Cardiff University. He undertook his PhD and postdoctoral work in synthetic medicinal chemistry under Professor Chris McGuigan, focusing on the design and synthesis of novel nucleosides and nucleotides as potential anticancer and antiviral drugs. With his appointment as lecturer in the Cardiff School of  Pharmacy and Pharmaceutical Sciences he strategically directed his research interests on the use of computer-aided techniques to design and discover novel anti-viral and anti-cancer compounds. In 2017, he was promoted to Professor and he continued to establish his reputation as an internationally recognised drug design expert in the antiviral and anticancer field. He is author on more than 130 peer-review papers and actively collaborates with several academic groups in the UK and the rest of the world. His focus to drug discovery and development emerges also from his strong connection with the private sector. He was a scientific consultant for the NASDAQ listed biotech Synergy Pharmaceuticals and for the NASDAQ listed biotech Inhibitex. He is an elected Board member of the International Society for Antiviral Research. In 2013, he was presented with the Young Researcher William Prusoff Award for his contribution to the antiviral field. Currently, he is also the Editor-in-Chief of Antiviral Chemistry and Chemotherapy

RAFFAELE DE FRANCESCO completed his studies in Biology in 1984 at the University of Milan. Subsequently, he was a postdoctoral fellow in the Biochemistry Department at Emory University, Atlanta, U.S.A., and in the Gene Expression Program at the European Molecular Biology Laboratory, Heidelberg, Germany. Between 1991 and 2008, Raffaele De Francesco worked at I.R.B.M./Merck Research Laboratory in Rome (Italy), where he led a group focusing on the identification of molecular targets for antiviral therapy and the development HCV enzymes inhibitors as novel agents for the treatment chronic hepatitis C. In 2008, he joined INGM as a Sr Group Leader. RDF is internationally recognized primarily for his pioneering work on the molecular virology of the hepatitis C virus (HCV) and for his key contributions to antiviral drug discovery and understanding of resistance to antiviral drugs. His early work in this area was pivotal in the identification of what became the most successful molecular targets of the new direct antivirals for HCV. In recognition of these contributions, RDF was assigned the 2018 EMBL Alumni Lennart Philipson Award. His current research interests focus on the identification of novel strategies for the eradication of chronic viral infection, such as chronic HBV and HIV infections. RDF has more than 140 papers published in peer-reviewed journal and a H-index of 64 (Scopus) and is inventor in many international patents.

SIMONA DISTINTO graduated in Pharmaceutical Chemistry at the University of Cagliari in 2003 and in 2003 won the “IN TIME 36” fellowship at the Athlone Laboratories, Ireland. She finished in 2006 her Ph.D. in Technology and Legislation of Drugs and Bioactive Molecules at University of Cagliari. From 2006 to 2008 she was post-Doc fellow at University of Catanzaro and then at  University of Innsbruck. From 2008 to 2010 she was  Senior Application Scientist at Inte:ligand Software- GmbH, the company that held and constantly develops the Inte:Ligand Software Entwicklungs und Consulting GmbH that supports scientists worldwide with innovative approaches for early drug discovery research by developing and applying computer-aided design (CAD) solutions. In  2008- 2009 Simona Distinto was Assistant Professor University of Innsbruck, nd from 2009 to 2011 Young Researcher FIRB University of Catanzaro, form 2010-2011 Adjunct Professor University of Catanzaro and from 2012 to 2016 Assistant Professor University of Cagliari. Form 2017 to present she is Associate Professor of medicinal chemistry at the University of Cagliari where she is leading the Computer Aided Drug    Design Section of the Department of Life and Environmental Sciences. Her expertise is mainly directed towards the field of computational medicinal chemistry. She has several undergoing projects based on the application of different approaches to the virtual screening and rational design of new drugs directed towards several targets, mainly involved in viral infections, cancer therapy and neurodegenerative diseases.  Simona Distinto  is co-autor of 55 scientific papers and collaborates as reviewer of several leading journals of Pharmaceutical Chemistry.

JOSE ESTE is a Senior Researcher and Head of the HIV Pathogenesis Laboratory of the AIDS Research Institute-IrsiCaixa, Hospital Germans Trias i Pujol in Badalona (Barcelona), Spain. He received a BSc. degree in Biology from University of Western Ontario, a Masters degree in Biochemistry from the Venezuelan Institute of Scientific Research and a PhD degree in Medical Science from the Katholieke Universiteit Leuven. Jose’s research interests include virus-cell interactions, HIV entry, antiviral drug-resistance, antiviral drug design and evaluation. His group also provides support to clinical trials in the HIV Unit of Hospital Germans Trias i Pujol. José Esté is the president of the International Society for Antiviral Research (ISAR), he is an editor for Antiviral Research and is on the editorial boards of the Journal of Biological Chemistry and Antimicrobial Agents and Chemotherapy. José Esté has coauthored over 160 peer-reviewed publications and review articles and serves in different Spanish and international review boards and evaluation committees.

REUBEN HARRIS Dr. Harris is a Professor of Biochemistry, Molecular Biology and Biophysics, the Associate Director of the Institute for Molecular Virology, and a Member of the Masonic Cancer Center at the University of Minnesota. He received his B.S. (1993) and Ph.D. (1997) degrees from the University of Alberta and performed postdoctoral work at Baylor College of Medicine (1997-1998), Yale University (1998), and Cambridge University (1998-2003). He joined the University of Minnesota as an Assistant Professor in 2003 and was promoted to Associate Professor with Tenure in 2008 and to Full Professor in 2013. Dr. Harris has received numerous grants and awards, including a Searle Scholarship, membership to the American Academy of Microbiology, and a Distinguished McKnight University Professorship. In 2015, he was also appointed as a Howard Hughes Medical Institute Investigator. Dr. Harris is an Associate Editor for Science Advances and an Editorial Board Member for Journal of Biological Chemistry, Journal of Virology, and Cancer Research. He has published over 160 manuscripts, contributed to 13 patent applications, and co-founded a cancer therapeutics company. Dr. Harris’s scientific passion is elucidating mechanisms of mutation and establishing relevance to human biology and disease. As a doctoral student, he discovered a novel recombination-dependent mutation process operative in stationary-phase bacteria with implications for antibiotic resistance and microbial evolution. As a postdoctoral fellow, he helped solve an immunology Rosetta stone by discovering the DNA cytosine deaminase activity of AID and proposing a DNA deamination model for antibody gene diversification. Also as a postdoctoral fellow, he discovered the DNA cytosine deaminase activity of several APOBEC family members and, during the transition to faculty, elucidated a new mechanism of antiviral immunity by demonstrating APOBEC3G-catalyzed retroviral cDNA hypermutation. As a Principal Investigator, Dr. Harris has become known for his work on APOBEC enzymes in antiviral immunity, including discovering multiple APOBEC3s in HIV-1 restriction, demonstrating the mechanism by which HIV-1 Vif degrades APOBEC3 proteins, and elucidating the first structures of APOBEC-ssDNA and APOBEC-RNA complexes. This body of work has shed light on fundamental mechanisms of antiviral immunity and yielded new strategies for drug development. In recent years, Dr. Harris’s virology studies have also enabled a major breakthrough in cancer research. His group found that APOBEC3B and APOBEC3H are responsible for a large proportion of mutations in breast, head/neck, lung, bladder, cervical, and other cancers. Independent work has confirmed these results and indicated that “APOBEC mutagenesis” far exceeds most other sources of mutations in cancer, including those attributable to smoking and UV rays. This breakthrough has created new opportunities for cancer diagnosis, prognosis, and treatment by targeting tumor evolvability. Please see http://harris.cbs.umn.edu for more information on Dr. Harris’s research program.

MICHELLE HASTINGS. Dr. Michelle Hastings, Ph.D., is an Associate Professor of Cell Biology and Anatomy and Director of the Center for Genetic Diseases at the Chicago Medical School at Rosalind Franklin University of Medicine and Science. Dr. Hastings earned an undergraduate degree in biology from St. Olaf College and a Ph.D. in biology/genetics from Marquette University.  She was a postdoctoral and senior fellow at Cold Spring Harbor Laboratory before joining the faculty at the Chicago Medical School at Rosalind Franklin University where she is currently the Director of the Center for Genetic Diseases and an Associate Professor of Cell Biology and Anatomy. Dr. Hastings’ lab studies RNA splicing and the ways this process can go wrong in disease and can be therapeutically manipulated. In particular, she studies RNA processing in neurodegenerative disease including Batten disease, spinal muscular atrophy, Usher syndrome, Alzheimer’s and Parkinson’s disease. A major focus of her work is on developing therapeutic approaches to treat these disorders using antisense technology. Her studies on Usher syndrome led to the first demonstration that hearing can be recovered in mice with a mutation that causes congenital deafness in humans.

ZLATKO JANEBA earned his Ph.D. in Organic chemistry from the Institute of Organic Chemistry and Biochemistry (IOCB) in Prague, part of the Czech Academy of Sciences. He underwent postdoctoral research training in the groups of Prof. Morris J. Robins at Brigham Young University and Prof. Paul F. Torrance at Northern Arizona University. He spend 3 years (March 2005 – February 2008) as senior scientist at Moravek Biochemicals, Inc. in California, one of the leading companies in the field of custom synthesis of radiolabeled compounds for pharmaceutical research. In 2008 he rejoined the research team of Prof. Antonín Holý at IOCB and in March 2010 he established his Junior Research Group at the same institution. Since January 2016, he is the head of the Senior Research Group at IOCB. Current research of the group involves design, synthesis and SAR studies of modified nucleosides and nucleotides, as well as other heterocyclic compounds, with a wide range of biological properties, especially antiviral, anticancer, antibacterial, anti-parasitic, and anti-inflammatory. Co-author of about 80 research papers with some 770 citations, h-index 16 (WoS), several patents. Member of International Society for Antiviral Research (ISAR), International Society of Nucleosides, Nucleotides and Nucleic Acids (IS3NA) and International Society of Heterocyclic Chemistry (ISHC). Dr. Janeba is an associate editor of Antiviral Chemistry & Chemotherapy and serves as a Vice-chairman of the IOCB Supervisory board and of the Supervisory board of IOCB TTO.

STUART LE GRICE received his Ph.D. from the Department of Biochemistry, University of Manchester, UK, in 1976, where he studied the mechanisms of R-factor-mediated multidrug resistance in Escherichia coli. After postdoctoral training in the United Kingdom, Germany, and the United States, he was appointed Senior Scientist in the Central Research Units of Hoffmann La Roche, Basel, Switzerland, where he worked from 1984 to 1990 evaluating HIV-1 and HIV-2 enzymes as therapeutic targets. In 1990, he joined the faculty in the Division of Infectious Diseases, Department of Medicine, Case Western Reserve University (CWRU), Cleveland, OH. Initially recruited as an Associate Professor of Medicine, he was awarded tenure in 1992, and in 1995 was promoted to Professor of Medicine, Biochemistry, and Oncology. From 1994 to 1999, he served as Director of the NIH-funded CWRU Center for AIDS Research. Dr. Le Grice joined the National Cancer Institute in 1999 as Chief of the Resistance Mechanisms Laboratory in the HIV Drug Resistance Program, Center for Cancer Research (CCR), and in 2005 was appointed to the Senior Biomedical Research Service. In 2006, he was appointed Head of the Center of Excellence in HIV/AIDS & Cancer Virology, CCR. He is a member of the CCR HIV and Cancer Virology faculty, Chemistry and Biology faculty, and the Steering Committee of the Molecular Targets Discovery Program. In addition to serving on the Editorial Board of the Journal of Biological Chemistry, Dr. Le Grice has been an ad hoc (1990-1999) and permanent Study Section member of NIH AIDS review panels (2000-2004), as well as an ad hoc reviewer for several international funding agencies.

STEPHAN LUDWIG obtained his PhD in 1993 at the Institute of Virology of University of Giessen, Germany. After the Habilitation (2000) in Molecular Biology at the Julius-Maximilians-Universität Würzburg, he was research assistant at the Institute of Virology, University of Giessen (1993-1994). In 1995 he became group leader at the Institute for Medical Radiation and Cell Research (MSZ), University of Wuerzburg, from 2001 to 2002 he earned a senior research fellowship at the MSZ. Stephan Ludwig was University Professor at the Institute of Molecular Medicine (IMM), University of Duesseldorf (2002-2004). Since 2004 he is University Professor and Director at the Institute for Molecular Virology (IMV) at the Center for Molecular Biology of Inflammation (ZMBE), University of Muenster. He was Managing Director of ZMBE  from 2006-2008 and Vice-Rector for Research at the University of Muenster from 2009-2016. He coordinates several research networks, such as the nationwide influenza research network “FluResearchNet” (since 2007; initiated and supported by the German Ministry for Education an Research – BMBF) and the “National Research Platform for Zoonoses ” (since 2009; initiated and supported by the BMBF). The Research at the Institute of Molecular Virology focusses on intracellular signal transduction pathways and their impact on viral infection and inflammation with a major interest for influenza viruses. Via gathering knowledge about the cellular processes which control virus replication and inflammatory responses, his work aims at identifying novel strategies against infectious and inflammatory diseases.

THOMAS MERTENS studied Chemistry in Bonn and Medicine in Cologne (1968-1976). He obtained the MD Thesis (Dr. med.) on 1976 and his Habilitation on 1984. Thomas Mertens was medical assistant, training in internal medicine and surgery (1976–1977); he continued with a research fellowship for the postdoctoral training in immunology, virology and diagnostics, Institute of Virology, University of Cologne (1977–1985). In 1983 he reached the Board Certification in Microbiology and Epidemiology of Infectious Diseases. In 1985 he became Professor (C2) at the Institute of Virology, University of Cologne, from 1991 to 1998 he was Professor (C3), in the Dept. of Virology, Ulm University. He was Temporary Director of the Dept. Medical Hygiene, Ulm University Hospital from 1991 to 1992; and Dean of Studies at the Medical Faculty, Ulm University from 2003 to 2006. Since 1998 he is the Director of the Institute of Virology at the Ulm University Hospital. His research focuses: mechanisms of resistance of antiviral substances towards herpes viruses; the analysis of the biological function of the viral gene UL97; new targets for antiviral interference against human cytomegalovirus (HCMV); molecular mechanisms and functional relevance of host-cell genes modulation by HCMV; viral tegument proteins and Morphogenesis of HCMV; new organ culture model for analysis of HCMV infection; the characterization and function of G-protein coupled receptor homologs of HCMV; and the Clinical Virology.

GIORGIO PALÙ received his M.D. degree from the University of Padova (1973) and the Specialty diplomas in Oncology (1976) and General Pathology (1978) from the University of Pavia. He worked as a Postdoctoral Fellow and Research Associate at the Tumor Institute, Jules Bordet, Université Libre, Bruxelles (1975), the Chester Beatty Research Institute-Royal Marsden Hospital, Royal Cancer Institute, London University, UK (1976-79), the Department of Pharmacology, Yale University, New Haven, CT (1980).Assistant Professor in Microbiology, University of Parma (1980-82); Associate Professor in Virology, University of Padova (1983-1989); Visiting Professor, Department of Molecular Biochemistry and Biophysics, Yale University, 1982,1984,1986; Division of Virology, National Institute for Medical Research, Mill Hill, London, UK, 1980,1985,1987; Division of Human Retrovirology, Dana Farber Cancer Institute, Harvard Medical School (1990), Full Professor of Microbiology and Virology (since 1989), University of Padova. Director at the University of Padova: Institute of Microbiology (1991-1999); Department of Histology, Microbiology and Medical Biotechnologies, (1999-2002); Department of Molecular Medicine (since 2012); Head of the Padova GMP Cell-factory and of the Unit of Clinical Microbiology and Virology, Padova University Hospital (since 1996). Coordinator, PhD Course/School in Virology (since 1998) and in Biomedicine (since 2007); Member of the Board of the International PhD Programmes in Molecular Medicine, University of Ulm, Germany (since 2008), in Biomedicine and Translational Neurosciences, Temple University, Philadelphia, USA (since 2011); Adjunct Professor at the Medical School and at the Faculty of Sciences, University of Temple; Pro-Rector, University of Padova (2002-2004); Dean, Faculty of Medicine, University of Padova (2004-2011). GP has also served as a member of the scientific-technical Committee of the Italian Drug Agency (AIFA), of the directory Board of the Italian AIDS Commission, of the Istituto Superiore di Sanità (Rome) and of the Institute of Human Virology (Baltimore). Professor Palù is the running President of the European Society for Virology. Giorgio Palù has long-standing experience in the study of pathogenesis of viral infections and the design of viral and non-viral vectors for gene transfer, somatic gene therapy and vaccinology. He has made relevant contributions to the study of antimicrobial therapy and resistance and anticancer therapy with more than 400 publications and 10 patents. His basic research has provided a platform for finding new targets for antiviral therapy and new antivirals based on peptides and small molecules able to disrupt the interface of protein-protein interactions essential for viral replication.

VINCENZO SUMMA  Head of Chemistry  IRBM Science Park spa from February 2010. IRBM Science Park is a research centre formally a spin-off of the Merck Research Laboratories locate in Rome. He graduated in  Chemistry at Università degli Studi di Roma ‘La Sapienza’ in 1991 and in 1996 obtained his Ph.D in Organich Chemistry at Bergische Universität Wuppertal. From 1992 to 1994  was researcher at University of Rome “La Sapienza” . He became Research Fellow Merck  from  March 1996 to  August 2001 . Here was promoted Senior Research Fellow (September 2001 );Senior Investigator Merck  (November 2005 ) and Director in the medicinal chemistry department  from November 2007to October 2009. From June 2010 is  Associate Researcher CNR-ITB National Research Council – Institute for Biomedical Technologies and from April 2013  Member of the Board of Directors at CNCCS Consortium (IRBM SP – Consiglio Nazionale delle Ricerche – Istituto Superiore di Sanità)