Emerging deadly viruses and their glycoproteins - From infection to vaccines and antivirals
2021 Women in Science Speaker Award
Genetic diversity and evolution of herpesviruses
Graciela Andrei holds a PhD in Biological Sciences from the Faculty of Sciences, University of Buenos Aires, where she received a fellowship from the National Research Council (1984-1989). She undertook a post-doctoral training on antiviral chemotherapy under Prof. Eric De Clercq with focus on herpesviruses, at the Rega Institute and was recipient of a KU Leuven fellowship (1989-1996). In 1997, she performed a visiting research training at the Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham and was appointed associate researcher at the Rega Institute (1997-2005). In 2005, with her appointment as assistant professor at the Faculty of Medicine, KU Leuven in Belgium, she directed her research interest on chemotherapy of viral diseases, with emphasis on different herpesviruses, poxviruses, polyomaviruses and papillomaviruses. In 2008, she was promoted to Associate Professor and her research is currently directed to the investigation of the molecular mechanism of action of antiviral drug resistance and pathogenicity of viral mutants, competitive fitness of drug-resistant viruses, three-dimensional culture models for the study of viral pathogenicity and antivirals efficacy (including SARS-CoV-2), the development of novel strategies to target cancer cells and the tumor microenvironment, and the molecular mechanism of action of the anticancer activity of nucleotide analogues. In 2009, she participated to the setup of the translational research platform RegaVir for typing drug resistance among DNA viruses.
She has (co)authored more than 350 papers in international peer-reviewed journals and 6 book chapters. She has been a member of the International Society for Antiviral Research since 1989 and has served as Secretary during 2012-2019, and as member of several committees. She is part of the editorial board of Antiviral Research, Archives of Virology, Viruses, PLoS One, is main editor of the ‘Antivirals and Vaccines’ section within Frontiers in Virology, and serve as reviewer for various journals.
2021 Antonín Holy Memorial Award Recipient
The Long and Winding Road: 35 Years of HIV reverse transcriptase structure, mechanism, and successful anti-AIDS drug design
Eddy Arnold’s laboratory at the Center for Advanced Biotechnology and Medicine (CABM) and Rutgers University works to understand the structural and molecular basis of the chemistry underlying life, with a focus on studying human disease problems and applying the insights gained to the development of better treatments.
His research has profoundly influenced our understanding of the structure and biological function of viruses and their components. The cross-disciplinary research in Arnold’s group uses a broad swath of tools and techniques from molecular biology, protein chemistry and biochemistry, biophysics, virology, crystallography, cryo-EM, and computational chemistry.
Eddy’s work has illuminated fundamental molecular mechanisms of viral polymerase structure and function, infection and escape from antiviral drugs and immune surveillance, and protein-nucleic acid and protein-ligand interactions. His efforts in Michael Rossmann’s laboratory culminated in elucidating the structure of a common cold virus, the first animal virus described in complete atomic detail.
Eddy’s structure of HIV reverse transcriptase complexed with DNA, the first polymerase visualized with a relevant substrate, changed the landscape of the HIV/AIDS and polymerase biochemistry fields. Arnold’s longstanding collaboration with Stephen Hughes has resulted in extraordinarily diverse and innovative studies of HIV reverse transcriptase structure, function, inhibition, and resistance that have helped to make this critical enzyme the most thoroughly understood of any DNA polymerase.
Arnold’s efforts with legendary drug developer Dr. Paul Janssen, enabled the design and discovery of five anti-AIDS drugs that are broadly used for treating HIV-infected patients and are resilient to drug resistance. Arnold’s team developed the strategic flexibility hypothesis, which postulates that structural flexibility and compactness of inhibitors can overcome resistance mutations, a concept that can be applied to any disease target. His elegant analyses of the RT inhibition mechanisms by AZT and nevirapine have likewise spawned generalizable principles. Crystallographic fragment screening efforts identified novel allosteric inhibitory sites in HIV-1 reverse transcriptase and led to new classes of antiviral inhibitors targeting influenza virus endonuclease and HIV-1 integrase. Arnold’s work with Richard Ebright on multi-subunit bacterial RNA polymerase visualized aspects of transcription relevant to all living organisms and elucidated binding modes for multiple new classes of potential antibiotics.
A perspective on viral vaccine immunity and the issue of disease enhancement
Ann Arvin, MD, is the Lucile Salter Packard Professor of Pediatrics and Professor of Microbiology and Immunology, Stanford University. Dr. Arvin’s laboratory investigates the molecular virology of varicella zoster virus (VZV) pathogenesis. Her clinical research has focused on immune responses of infants and children to viral infections and vaccines, including VZV, measles and influenza vaccines, and herpes simplex virus and cytomegalovirus. She is a senior research advisor, Vir Biotechnology, and has consulted for several vaccine companies. Her committee service related to infectious diseases, vaccines and policy has included: NIAID Director’s Advisory Council; National Vaccine Advisory Committee; NAM (IOM) Committee on the Scientific Uses of Variola Virus, Chair; WHO Steering Committee on Research Related to Measles Vaccines, Chair; NIAID Blue Ribbon Panel on Influenza; President’s Council on Science and Technology Influenza Working Groups; NAS/NRC Committees on Policy and Global Affairs and Science, Technology and Law and Board on Life Sciences. She was chief of Infectious Diseases, Packard Children’s Hospital (1984-2006). Dr. Arvin is a fellow of the American Academy of Arts & Sciences, the National Academy of Medicine, the American Association for the Advancement of Science, the Academy of the American Society for Microbiology, the Association of American Physicians and the American Pediatric Society. She received degrees from Brown University (AB), Brandeis University (MA), and the University of Pennsylvania (MD) and postdoctoral fellowship training at the University of California, San Francisco and Stanford University School of Medicine.
Treating RSV infection
Louis Bont, MD, PhD, is Pediatrician Infectiologist-Immunologist and founding chairman of ReSViNET, an international respiratory syncytial virus (RSV) research consortium. His specific research interest is RSV pathogenesis and burden of disease. His work focuses on unraveling the role of neutrophils, RSV-related mortality and long-term airway disease following RSV infection. Dr. Bont is the lead investigator of the INFORM study, a large prospective global clinical virology study to unravel the molecular epidemiology of RSV in about 4000 children. He is one of the co-leads of the RESCEU consortium aiming to define the RSV burden of disease in Europe. He is leading the RSV GOLD mortality registry funded by the Bill and Melinda Gates Foundation. His group collaborates with the World Health Organization on RSV surveillance and vaccine development. Dr. Bont’s research focuses on clinical and translational mechanisms of disease and identifying targets for intervention of RSV bronchiolitis. He has been the lead author of about 200 publications in peer-reviewed medical journals. Dr. Bont is chairman of the Institutional Review Board at the University Medical Center Utrecht, the Netherlands and structural advisor of pharmaceutical companies. He founded the Training of Upcoming Leaders in Pediatric Science (TULIPS), a career training network for clinician scientists in the field of Child Health.
Antiviral agents for serious RNA virus infections; a personalised medicine approach
Judith Breuer is a Professor of Virology at UCL and Clinical lead for Virology at Great Ormond Street Hospital for Children. Her research interests include the development of high throughput pathogen sequencing directly from clinical material for the analysis of pathogen evolution and identification of pathogen genetic determinants of clinical disease. Professor Breuer has worked for many years evaluating on varicella zoster virus and its vaccine. Her work has elucidated many aspects of VZV natural history and pathogenesis. Professor Breuer’s use of combined host and viral transcriptomics uncovered the requirement of VZV replication for keratinocyte differentiation and identified new epidermal signalling pathways associated with replication not only of VZV but other skin viruses. The application of enriched transcriptomics to early post mortem human trigeminal ganglia led her group to discover the canonical VZV latency transcript. More recently Professor Breuer has developed diagnostic metagenomic methods for pathogen discovery in patients with undetected infections of the brain, widening this recently to other samples. through her clinical work she has developed a pipeline for the evaluation of new and repurposed drugs, including combinations for treatment of serious viral infections particularly in immunocompromised individuals. In the absence of data from clinical trials her work has focussed on a personalised medicine approach to characterising the efficacy of novel treatments using genomics, in vitro and in vivo pharmacokinetics, pharmacodynamics measurements complemented by animal models. The methods developed have been applied to studies of antivirals used to treat SARS-CoV-2. Professor Breuer chairs the Joint Committee on Vaccines and Immunisation Varicella zoster vaccine subcommittees and the Immunocompromised Working Group. Professor Breuer is a member of the UK MHRA Expert working group on Covid vaccines, the SAGE subcommittee on Hospital Onset Covid Infection and the COG-UK steering group.
2021 Diversity Award Recipient
My career-long fascination with antiviral therapeutics
Craig E. Cameron is the Jeffery Houpt Distinguished Professor and Chair of the Department of Microbiology and Immunology at the University of North Carolina School of Medicine. He earned a Bachelor of Science degree in chemistry from Howard University in 1987. Following doctoral studies in biochemistry at Case Western Reserve University School of Medicine and post-doctoral studies in the chemistry department at Penn State, Cameron joined the faculty of biochemistry and molecular biology at Penn State in 1997. He was tenured, promoted to the rank of associate professor and appointed Louis Martarano Associate Professor in 2002. In 2005, he was promoted to the rank of professor and named the Paul Berg Professor of Biochemistry and Molecular Biology. From 2011-2012, Cameron served a two-year term as Associate Head for Research and Graduate Education. In 2013, he was named holder of the Eberly Family Chair in Biochemistry and Molecular Biology. Cameron moved to his current position in Chapel Hill in the fall of 2019. Cameron’s research focuses on RNA polymerases and RNA-binding proteins required for viral replication or mitochondrial function. The goal of this work is development of novel strategies to treat and/or prevent viral infections and mitochondrial dysfunction. During his career, Dr. Cameron has received several honors, including the Howard Temin Award from the National Cancer Institute, an Established Investigator Award from the American Heart Association, a Distinguished Service Award from the Eberly College of Science Alumni Association, the Genesis Scholar Award from HBCU Digest, Fellow of the American Association for the Advancement of Science, and Fellow of the American Academy of Microbiology. Cameron currently serves as an associate editor for Journal of Biological Chemistry and Science Advances. In July 2020, Cameron became president of the American Society for Virology.
The SARS-CoV1 and 2 replication/transcription machinery and its future for drug-design
Dr. Bruno Canard of the University of Marseille, France, obtained his PhD in Microbiology from the University of Paris VII, at the Pasteur Institute under the guidance of Dr. Stewart T. Cole. After post-doctoral training at Harvard Medical School in 1995-1998 under the guidance of Pr. Charles C. Richardson, he started his team with an ATIPE-CNRS grant in 1998 in the laboratory of Architecture et Fonctions des Macromolécules Biologiques (UMR 7257 CNRS-Aix Marseille University). Dr. Bruno Canard is an expert in the study of emerging RNA virus enzymes and drug-design, in particular Human Immunodeficiency virus, Flavivirus (Dengue, Zika, West-Nile,...), Ebola virus, and since 2003, SARS-Coronavirus. He has trained 15 PhDs, co-ordinated the European Integrated Project project FP7 VIZIER in virology (24 partners, 12.9 M€). He is currently involved in several large scale European projects (SCORE, IMI-CARE) addressing the SARS-CoV2 virus. He has received the William Prusoff Award (2008) from the International Society for Antiviral Research. His team is supported, among others, by the Fondation pour la Recherche Médicale (2009-2011, and 2019-2021). He has published >220 peer-reviewed papers.
Development of small molecule protease inhibitors against SARS-CoV-2
Kyeong-Ok Chang received his DVM degree from Seoul National University, Seoul, KOREA and PhD degree from the Ohio State University, Columbus, OH. After post-doctoral training at NIH, he joined the College of Veterinary Medicine, Kansas State University, Manhattan, KS in 2005. He has over 25 years of research experience in the field of virology, specifically on viral pathogenesis and the development of therapeutic measures for important human and animal viral infections. One of his current research focuses is the identification of antiviral drug targets, development of in vitro assay systems and animal models for human coronaviruses including MERS-CoV, SARS-CoV and SARS-CoV-2. He has been actively collaborating in a multi-disciplinary team from the fields of virology, medicinal chemistry, structural biology, and drug development experts. Their major focus of the collaborative efforts is on protease inhibitors for viruses that encode 3C-like proteases (3CLpro). Through these drug development endeavors, they have identified multiple protease inhibitors including GC376 effective to multiple coronaviruses. These compounds are highly effective against human coronaviruses including SARS-CoV-2 in enzyme and cell culture and animal models.
Antivirals and preparedness for pandemics: what we have and what we need
Tomas Cihlar, PhD is a Vice President of Virology at Gilead Sciences with responsibility for coordinating preclinical antiviral research. Dr Cihlar joined Gilead after receiving his PhD in Biochemistry from the Institute of Organic Chemistry and Biochemistry in Prague, Czech Republic. While at Gilead, he has contributed to the development and regulatory approval of multiple antiviral products including the portfolio of Gilead’s HIV drugs and their combinations. Together with his colleagues at Gilead, he established research programs focused on long-acting antiretrovirals, cure of HIV and chronic hepatitis B, and treatment of respiratory and emerging viral infections. For several years, Dr Cihlar served as a leader of remdesivir program at Gilead. Remdesivir has been approved by FDA in October 2020 for the treatment of hospitalized COVID-19 patients. In past, Dr Cihlar served on the Board of Directors of the International Society for Antiviral Research and is currently on the Board of Directors of Global Virus Network.
Remdesivir treatment for emerging virus infections
Dr. Emmie de Wit is the Chief of the Molecular Pathogenesis Unit in the Laboratory of Virology of NIAID, where her lab focuses on emerging respiratory viruses, aiming to combine pathogenesis studies with detailed molecular analyses to identify molecular determinants of severe respiratory tract disease within the virus and the host. Dr. de Wit received her PhD in virology in 2006 from Erasmus University Rotterdam, the Netherlands. Her research there focused on the replication, pathogenesis and transmission of influenza A virus. In 2009, she moved to the Laboratory of Virology of NIAID in Hamilton, Montana to work in the biosafety level 4 laboratory there. Here, she focused on the pathogenesis of and countermeasures against Nipah virus, the Middle East Respiratory Syndrome Coronavirus and the 1918 H1N1 influenza A virus (Spanish flu). In 2014-2015, Dr. de Wit spent 4 months in a field lab in Monrovia, Liberia in charge of patient diagnostics for several Ebola Treatment Units in the area, to help contain the devastating Ebola epidemic in Liberia. Since the emergence of COVID-19, Dr. de Wit has focused her research on SARS-CoV-2, developing animal models and using those for testing of medical countermeasures and to gain a better understanding of SARS-CoV-2 pathogenesis.
Sequence-based design of small molecules targeting RNA
Dr. Matthew Disney is a Professor in the bicoastal Department of Chemistry at The Scripps Research Institute. He is an expert on the design, discovery, and development of small molecules that target disease-causing RNA for therapeutic benefit. Prof. Disney has developed novel strategies that provide a foundational understanding of RNA-small molecule interactions that enable design of bioactive small molecules targeting RNA in a transcriptome-wide manner and only from sequence. Indeed, his laboratory has discovered bioactive small molecules that target microRNAs involved in cancer (in situ and in vivo), addiction, and viral infections, including SARS-CoV-2 and hepatitis C virus (HCV). Collectively, his interdisciplinary and innovative approaches, which combine biochemistry, biophysics, organic synthesis, and computation, has provided expedited routes to RNA-directed chemical probes of function or lead therapeutic modalities.
In recent work, Prof. Disney has devised a method to imbue small molecules with the ability to cleave with targeted transcripts in living cells, drastically improving the activity of designer small molecules and ridding the cell of the disease-causing RNA. Dubbed ribonuclease targeting chimeras (RIBOTACs), his laboratory has shown that the small molecule hybrids can selectively cleave viral RNAs.Prof. Disney has received various awards for his innovative work, including the National Institute of Neurological Disorders and Stroke (NINDS) Research Program Award, the National Institutes of Health (NIH) Director’s Pioneer Award, Raymond and Beverly Sackler Prize in the Physical Sciences, BioFlorida’s Weaver H. Gaines Entrepreneur of the Year Award, Barry Cohen Prize, awarded by the Medicinal Chemistry Section of the Israel Chemical Society and Teva Pharmaceutical Industries, Tetrahedron Young Investigator Award, and a Finalist for the Blavatnik Award for Young Scientists, among others.
Scientific basis for the rapid development of highly effective RNA-based COVID-19 vaccines
Dr. Philip Dormitzer leads Pfizer viral vaccines research and development programs. These programs include the Pfizer-BioNTech RNA-based COVID-19 pandemic vaccine and influenza vaccine collaborations. The COVID-19 vaccine has been authorized for emergency use, and mass vaccination campaigns are in progress around the world. A prefusion F-based RSV vaccine to protect infants through maternal immunization has been advanced from discovery to a global phase 3 clinical trial in pregnant women. A cytomegalovirus vaccine candidate is preclinical. Before joining Pfizer, Dr. Dormitzer held positions at Novartis Vaccines that included Head of US Research. He was the founding member of the Novartis Viral Vaccine Research Center in Cambridge, MA. In 2009, his research team supported the development and licensure of three H1N1v influenza pandemic vaccines in what remains the most rapid vaccine response in history. In 2013, his team responded to the H7N9 influenza outbreak by supplying the US pre-pandemic stockpile with a vaccine generated from a synthesized virus. Before joining industry, Dr. Dormitzer was an Assistant Professor of Pediatrics at Harvard Medical School and led a structural virology laboratory, which, with collaborators, determined the structures of the rotavirus neutralization antigens. He graduated summa cum laude in Anthropology from Harvard College; conducted paleontological research in Pakistan and studied the Efe Pygmies in Zaire; obtained a Ph.D. in Cancer Biology and an MD at Stanford University; completed Internal Medicine training at Massachusetts General Hospital; and completed the Harvard Infectious Diseases Program clinical fellowship.
2021 William Prusoff Memorial Award Recipient
Mid-term report on my academic journey to discover novel HBV/HDV therapeutics
David Durantel obtained his PhD in Molecular and Cellular Virology at the University of Montpellier in 1997. After three postdoctoral trainings respectively at Oxford Brookes University (with Pr Linda King and Robert Possee, UK), University of Oxford (with Pr Raymond Dwek and Dr Nicole Zitzmann, UK), and INSERM (National Institute for Health and Medical Research; with Pr Fabien Zoulim), he obtained a tenured position in 2005 at INSERM, then his Habilitation to direct research in 2008 from the University of Lyon (UCBL), and was finally promoted Director of Research in 2016. During all these years, he worked on numerous research projects related to drug discovery (on both Direct Acting (DAA) and Host-Targeting Agents (HTA)) in the viral hepatitis field. He currently leads a team at the International Center for Research in Infectiology (CIRI, http://ciri.inserm.fr/; Lyon), which studies HBV and HDV infections/co-infections and contributes to the R&D of novel DAAs and HTAs. He has authored/coauthored 110 PubMed-recorded articles/reviews, as well as numerous proceedings/book chapters & is an inventor in several patents. He acts as reviewers for many journals, including Gastroenterology, Gut, Hepatology, J. Hepatol, PlosPathogen, antiviral journals, et caetera…
Since 2014, he has been the associate editor for the Antiviral Research journal, section viral hepatitis, and, associated to this function, has co-organized several international antiviral conferences. He was recently nominated to organize the 2022 edition of the International HBV meeting.
He contributes to the French coordination on viral hepatitis research at ANRS (French Agency for AIDS and Hepatitis Research), holds seats on the boards of several ANRS “study section” and “concerted action” committees and routinely organizes excellent workshops/conferences at the National level. He was member of the executive board of the French Association for Liver Studies (AFEF) between 2015-2018, and is an active member of the European Association for the Study of the Liver (EASL).
The polymerase complex of the non-segmented negative strand RNA viruses: differences in initiation mechanisms
Rachel Fearns, PhD is a Professor of Microbiology at Boston University School of Medicine. Her research focuses on understanding the transcription and genome replication mechanisms of respiratory syncytial virus (RSV) and other non-segmented negative strand RNA viruses. Transcription and genome replication are highly complex processes, involving multiple different steps. However, despite their complexity, both transcription and genome replication are performed by the same viral RNA dependent RNA polymerase. Her group has developed cell-based assays that allow different events in RSV transcription and RNA replication to be dissected. They also developed assays in which RNA synthesis is reconstituted in vitro using purified polymerase protein and an RNA promoter template to investigate events that occur during polymerase-promoter interactions. The development of these different assays has allowed them to elucidate RNA and protein features that enable transcription and replication initiation, mRNA capping, and mRNA and replicative RNA elongation. In addition to addressing basic research questions, because of their expertise in studying the RSV polymerase, pharmaceutical companies and academic groups have sought their collaborative support to study mechanisms of inhibition by small molecule polymerase inhibitors. In more recent work, her group has begun to extend the techniques they developed for RSV to other RNA viruses, including the pneumovirus, human metapneumovirus, the paramyxovirus, parainfluenza virus type 3 and the filovirus, Marburg virus. They are currently comparing the transcription and replication mechanisms of these different viruses. They anticipate that a detailed mechanistic understanding of their similarities and differences will help explain inhibitor specificity and identify strategies for inhibition by broad-spectrum antivirals.
Now that we have the world’s attention: Influenza!
Ron Fouchier is professor in Molecular Virology at Erasmus MC Rotterdam. He obtained a PhD in 1995 for HIV/AIDS research at the University of Amsterdam with Hanneke Schuitemaker and continued HIV work at the University of Pennsylvania as a postdoc with Michael Malim. Late 1998 he started a Molecular Virology research line on respiratory viruses, in particular influenza, at Erasmus MC in the department headed then by Ab Osterhaus. Ron’s team contributed substantially to the identification and characterization of various “new” viruses, such as human metapneumovirus, human coronavirus NL63, SARS coronavirus, MERS coronavirus, and influenza A virus subtype H16. Currently, his research is focused on respiratory viruses of humans and animals, antigenic drift, and influenza virus zoonoses, transmission and pandemics. Fouchier is elected member of the Royal Dutch Academy of Sciences (KNAW), the Royal Holland Society of Sciences and Humanities (KHMW) and Academia Europeae. In 2006 he received the Heine-Medin award of the European Society for Clinical Virology and in 2013 the Huibregtsen award for top innovative science with societal impact. Fouchier is a web-of-science Highly Cited author.
Towards combination treatments for Chronic Hepatitis B: an immunologist’s point of view
Adam Gehring received his PhD at Case Western Reserve University in Cleveland, Ohio. His training included a Postdoctoral Fellowship in the Institute of Hepatology at University College London and a position of Senior Research Fellow, and subsequently Assistant Principal Investigator, at the Singapore Institute for Clinical Sciences with Antonio Bertoletti. During his postdoctoral training Dr. Gehring was instrumental in developing TCR gene therapy for chronic HBV. His foundational work resulted in human application of engineered T cells for HBV-related HCC tumors expressing viral antigen. Dr. Gehring moved to Saint Louis University as an Assistant Professor in the Molecular Microbiology and Immunology department in March 2013 before joining the Toronto Center for Liver Disease as Biology Lead in February 2016.
Dr. Gehring runs a translational HBV immunology research lab focused on liver pathogenesis and sex-based differences in disease progression. His primary interest lies in defining the mechanisms driving liver inflammation during HBV-related flares using functional and transcriptomic approaches in liver biopsies. He has established an internal immune monitoring core within his lab to process and analyze immune responses in Phase 2 clinical studies for HBV.Dr. Gehring is currently Co-Chair for the Immune Monitoring Workgroup of the HBV Forum. He is Co-Chair for the International HBV Meeting being organized in Toronto in September, 2021.
The ABCs of rhinovirus infections and asthma
James E. Gern, MD FAAAAI is a Professor of Pediatrics and Medicine at the University of Wisconsin School of Medicine and Public Health in Madison. Dr. Gern earned his MD degree from the University of South Florida and completed pediatrics training at the State University of New York in Syracuse and at Tufts University in Boston. After serving as a general pediatrician in the US Navy for three years, he completed an Allergy/Immunology Fellowship at Johns Hopkins University in 1992, and then joined the faculty at the UW-Madison. He is currently the Chief of the Allergy, Immunology and Rheumatology Division, and the Vice Chair for Research in the Department of Pediatrics. Dr. Gern’s research focuses on identifying how viral respiratory infections and other environmental and host factors promote the development of childhood asthma and acute exacerbations of this disease.
New Strategies for Modeling and Treating Emerging Viral Pathogens
Dr. Mark Heise is a Professor in the Departments of Genetics and Microbiology and Immunology within the University of North Carolina School of Medicine. Dr. Heise received his BA in Biology from St. Olaf College in 1991 and his PhD in Immunology from Washington University in St. Louis in 1996. He conducted post-graduate research at the University of North Carolina in Chapel Hill on viral pathogenesis from 1997 to 2000, prior to joining the faculty at UNC.
The Heise laboratory uses molecular virology, immunology, biochemical, and quantitative genetics methodologies to understand the biology and pathogenesis of emerging alphaviruses, coronaviruses, and influenza viruses, with the goal of using this information to facilitate the development of safer and more effective vaccines and antiviral therapies against these pathogens. Dr. Heise’s group has also been at the forefront of developing animal models of virus-induced disease and then using those models to develop and test antivirals and vaccines against emerging alphaviruses and coronaviruses. His laboratory has also been a leader in the use of systems genetics methods to identify and study polymorphic host genes that regulate susceptibility to viruses such as chikungunya virus and influenza A virus.
HSV-1 and Alzheimer’s Disease: causation or association? Understanding the biologic plausibility
Dr. Christine Johnston is an Associate Professor in the Division of Allergy and Infectious Diseases, Department of Medicine at University of Washington. She is an infectious diseases physician who performs clinical studies of herpes simplex virus (HSV) infection focusing on the intersection between viral pathogenesis and host immune responses, with the ultimate goal of developing successful vaccines and medications to prevent and treat HSV infections. Dr. Johnston’s prior research has focused on HSV infections in the genital tract, utilizing daily genital swabs to identify localized anatomic regions of viral shedding and to perform biopsies at these sites to characterize the immune response to asymptomatic HSV-2 shedding. She has also conducted a prospective study of the natural history of genital HSV-1 infection. In addition, she is pursuing studies to understand associations between HSV-1 and Alzheimer’s Disease. She is also the Medical Director of the University of Washington STD Prevention Training Center, which is part of the CDC-funded National Network of STD Clinical Prevention Training Centers (NNPTC) and the Associate Program Director for the University of Washington Infectious Disease Fellowship Training Program.
Four-segmented Rift Valley fever virus as a novel live-attenuated vaccine for animal and human use
Jeroen Kortekaas is affiliated with Wageningen Bioveterinary Research (WBVR), Lelystad, the Netherlands. His research focuses on Rift Valley fever virus (RVFV) and other members of the order Bunyavirales, with an additional interest in zoonotic arboviruses of the families Togaviridae and Flaviviridae. He collaborates with several universities and research institutes around the world (Germany, US, South Africa, China). He has (co)authored more than 60 publications in peer-reviewed scientific journals and 6 patent applications. Apart from his involvement in vaccine development and fundamental studies on arboviruses, he is an ad hoc member of several Rift Valley fever expert panels. He is currently coordinator of two large, international projects, focused on the development of veterinary and human RVF vaccines. The latter LARISSA project ( https://www.larissa.online/) is funded by the Coalition for Epidemic Preparedness Innovations (CEPI). In 2017, he became CSO of BunyaVax (www.bunyavax.com), a company that develops vaccines using proprietary platform technologies. In the same year, he was appointed special professor of the Laboratory of Virology of Wageningen University. He is also member of the Netherlands Commission on Genetic Modification (COGEM) and member of the board of the Virology Division of the Royal Dutch Society for Microbiology.
Antibody responses to the SARS-CoV-2 spike protein
Florian Krammer, PhD, graduated from the University of Natural Resources and Life Sciences, Vienna (Austria) in 2010. He received his postdoctoral training in the laboratory of Dr. Peter Palese at the Icahn School of Medicine at Mount Sinai, New York working on hemagglutinin stalk-based immunity and universal influenza virus vaccines. In 2014 he became an independent principal investigator and is currently Mount Sinai Professor of Vaccinology at the Icahn School of Medicine at Mount Sinai. Dr. Krammer's work focuses on understanding the mechanisms of interactions between antibodies and viral surface glycoproteins and on translating this work into novel, broadly protective vaccines and therapeutics. The main target is influenza virus but he is also working on coronaviruses, flaviviruses, hantaviruses, filoviruses, and arenaviruses.
2021 Gertrude Elion Memorial Award Recipient
Defining innovation in the quest for treatment, prevention and cure of viral diseases
Dr. William “Bill” Lee is the Executive Vice President of Research at Gilead Sciences. He received his BS in Chemistry from the University of Massachusetts at Amherst and a PhD in Organic Chemistry with Teddy Traylor from the University of California San Diego. He did postdoctoral work in photocatalysis with Michael Gräzel at the EPFL in Switzerland and in bio-organic chemistry with Tom Bruice at the University of California Santa Barbara. He began his industry career at Syntex Research in Palo Alto, California and then moved to California Biotechnology where he was head of Drug Delivery. In 1991 he joined Gilead Sciences as Director of Pharmaceutical Product Development and became head of Discovery Research in 2000. During his tenure, Gilead has radically changed the paradigm for both treatment and prevention of HIV, launching multiple single-tablet regimens; discovered and developed curative antiviral regimens for HCV; and in 2020, received approval for the first antiviral drug, Veklury® against the SARS 2 virus. Dr. Lee is a co-inventor of Cellcept®, Viread® and tenofovir alafenamide, a lymphatic targeting prodrug of tenofovir, approved for the treatment and prevention of HIV in the combination products Genvoya®, Descovy®, Biktarvy®; Odefsey® and Symtuza® and as a solo product, Vemlidy® for the treatment of HBV®.
Biologics as therapeutics for rapid outbreak response - can we get there fast enough?
Associate Professor Jenny Low is a Board-Certified senior consultant with the Department of Infectious Diseases in Singapore General Hospital and faculty at the Programme in Emerging Infectious Diseases, Duke-NUS Medical School. Concurrently, she is the co-director of the Viral Research and Experimental Medicine Centre@ SingHealth Duke-NUS (ViREMiCS) in the SingHealth Duke NUS AMC and deputy clinical director at the SingHealth Investigational Medicine Unit (IMU). She led the early dengue infection and outcome (EDEN) study in Singapore that detailed, in several publications, clinical dengue in adults. She was the lead clinical investigator in the first proof-of-concept clinical trial on the use of Celgosivir as an anti-dengue drug (CELADEN) in Singapore. She was also the lead PI in an investigator led trial which tested the role of pre-existing cross-reactive antibodies and authenticated antibody dependent enhancement and in flaviviral infections in a human experimental study using 2 different flaviviral vaccines. Her current research focus is on early phase adaptive clinical trials of viral therapeutics and vaccine development for rapid response as well as the role of the innate immune response in modulating the outcome of infection or vaccination thereby improving therapeutic interventional strategies for infectious diseases. She has conducted several novel monoclonal antibodies phase 1 trials against viruses including Zika, Yellow fever and SARS-COV2 viruses. She is twice awarded the National Clinician Scientist Award by the Ministry of Health, Singapore in 2016 and 2019 for her to study these urgent unmet clinical needs.
Design of nucleotide prodrugs for antiviral chemotherapy – the TriPPPro-Approach
Chris Meier obtained a diploma and a doctorate (PhD) in Chemistry from the University of Marburg, Germany for a thesis on the synthesis of ultimate carcinogens involved in the induction of the chemical carcinogenesis. He joined the Organic Chemistry Department at the Pasteur-Institute in Paris, France as a Post-Doc and started working on antivirally active nucleosides and prodrugs. In 1996 he received the Habilitation in Organic Chemistry from the University of Frankfurt/Main, Germany under the mentorship of Prof. J. Engels. He was appointed as associate professor at the University of Würzburg, Germany, and in 1999 he joined Universität Hamburg, Germany as a full professor. He is the current past-president of the International Society on Nucleoside, Nucleotides and Nucleic Acids (IS3NA) and is the Scientific Director of the Centre for Structural Systems Biology (CSSB) in Hamburg. He received the Prusoff-Award in 2007 and the Antonín Holy-Award in 2018 from the International Society on Antiviral Research (ISAR). He was awarded as a Zhiquiang-guest professor from Shanghai University. Chris’s research covers pronucleotide development (cycloSal-, DiPPro- and TriPPPro-approaches for the delivery of nucleotide analogues), general nucleoside chemistry, small molecule antivirals to target host cell factor to combat against Bunya viridae and hemorrhagic fever viruses, synthesis of membrane permeable and/or photocaged nucleotides, e.g. second messengers. He has published more than 250 scientific publications and is the inventor of 10 issued patents.
Pan-serotype dengue virus inhibitor that blocks the NS3-NS4B interaction and exhibits unprecedented in vivo potency
Johan Neyts is full professor of Virology at the University of Leuven, Belgium. He teaches virology at the medical school and at the school of dentistry. The lab has a long-standing expertise in the development of antivirals strategies and drugs against emerging and neglected viral infections such as dengue and other flaviviruses, Chikungunya and other alphaviruses, enteroviruses, noroviruses, HEV and rabies and is intensively involved in the search for antiviral strategies against SARS-CoV2. A second focus of the lab is the development of a novel vaccine technology platform technology based on the yellow fever virus vaccine as a vector; this include among others vaccines against rabies and SARS-CoV2. His team is also developing a technology, the PLLAV (Plasmid Launched Live Attenuated Virus); which allows to rapidly engineer highly thermostable vaccines against multiple viral pathogens. Johan is past-president of the International Society for Antiviral Research (www.isar-icar.com). Four classes of antivirals discovered in his laboratory have been licensed to major pharmaceutical companies (two on HCV, one on dengue and one on rhino/enteroviruses). He published >500 papers in peer reviewed journals and has given >240 invited lectures and a large number of lay-press interviews.
Targeting the proteases of SARS-CoV-2 and other RNA viruses
Christoph Nitsche studied chemistry and business administration. He obtained his PhD in 2014 from Heidelberg University, where his fascination for antiviral drug discovery began. In 2015, the German Chemical Society awarded him the PhD prize for medicinal chemistry for his work on inhibitors of the dengue virus protease. He worked as a Feodor Lynen Fellow (Alexander von Humboldt Foundation) at the Australian National University (2015–2018) and as a Rising Star Fellow at the Free University of Berlin (2018–2019). In 2019, he received a Discovery Early Career Research Award from the Australian Research Council to start his independent career at the ANU, where he was appointed Senior Lecturer in 2020. His research targets proteases from RNA viruses with a focus on dengue, West Nile, Zika, Chikungunya and SARS-CoV-2. His research operates at the interface between synthetic chemistry and biochemistry, designing selective probes and inhibitors that help to characterize and validate proteases as antiviral drug targets and develop lead compounds for drug discovery campaigns.
Understanding the multiple functions of the bunyavirus polymerase protein
Maria Rosenthal is leading a junior research group at the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, where her team uses structural biology, virology, biochemistry and molecular biology techniques to understand the genome replication and trancription of bunyaviruses, an important group of emerging RNA viruses. After studying human biology in Marburg with a focus on infection biology she obtained her PhD in virology and biochemistry from the University of Bremen. She solved several structures of bunyavirus polymerase protein domains by X-ray crystallography substantially contributing to the understanding of bunyavirus cap-snatching mechanism. In highly collaborative projects her group currently also applies cryo-EM single particle analysis in order to solve structures of full-length bunyavirus polymerase proteins. Additionally they use biochemical assays to investigate the different functions of bunyavirus polymerase. A profound structural and functional understanding of viral genome replication and transcription should ultimately lead to the identification of suitable targets for potentially broad-spectrum antivirals against the diverse group of bunyaviruses.
Janssen’s effort in the development of an Ad26 based COVID-19 vaccine
Hanneke Schuitemaker, PhD, is the Head of Viral Vaccine Discovery and Translational Medicine and Disease Area Stronghold Leader for Viral Vaccines at Janssen Vaccines & Prevention B.V. She has been in these roles since 2010 and oversees Janssen’s viral vaccine programs including investigational vaccine candidates for HIV, respiratory syncytial virus (RSV), Ebola, Zika, SARS-CoV-2 and HPV. In addition, she is a Professor of Virology at the Amsterdam University Medical Center.Hanneke Schuitemaker is a medical biologist by training, received her PhD in Medicine in 1992 at the University of Amsterdam and worked for more than 20 years on HIV-1 pathogenesis, first at Sanquin (1989-2007), the blood supply foundation in the Netherlands, where she was the Chair of the department of Clinical Viro-Immunology (1998-2007), and then at the Amsterdam University Medical Center (2008-2010), where she was the Chair of the Department of Experimental Immunology and a member of the Research Council. From mid-2003 to mid-2004, she worked as a visiting scientist at The Scripps Research Institute in La Jolla, California. She successfully trained more than 30 PhD students and co-authored more than 300 peer-reviewed scientific articles.
SARS-CoV-2 Biology and Countermeasure Development
Pei-Yong Shi is John Sealy Distinguished Chair in Innovations in Molecular Biology at University of Texas Medical Branch. He works on RNA virus replication, drug discovery, and vaccine research. His unique expertise in public health laboratory (New York State Department of Health), pharmaceutical companies (Novartis and Bristol-Myers Squibb), and academia (University of Texas Medical Branch, Yale, and other universities) allows his team to work on both basic and translational research. He has published over 300 peer-reviewed papers in leading journals, including Nature, Science, and Cell. In response to the COVID pandemic, his team published the first peer-reviewed infectious clone and reporter virus for SARS-CoV-2; these reagents have been shared around the world to fight COVID pandemic. Many of his technologies have been used in leading pharmaceutical companies for diagnostic and countermeasure development. A recent example is his reporter neutralization assay that has enabled the rapid development of Pfizer’s COVID-19 vaccine, the first vaccine with 95% efficacy in humans
Barriers to curing HIV infection
Robert Siliciano is a Professor of Medicine at the Johns Hopkins University School of Medicine. He is an immunologist and virologist recognized for his work on the treatment of HIV infection. He is known particularly for identifying and characterizing the latent reservoir for HIV in resting CD4+ T cells. This reservoir is the major barrier to curing HIV infection and the subject of an intense international research effort. Siliciano was born in Rochester, New York and grew up in Elmira, New York. He graduated from Princeton University with a degree in chemistry and then received an MD and a PhD in immunology from the Johns Hopkins University School of Medicine. After a postdoctoral fellowship in immunology at Harvard Medical School, he joined the faculty of the Johns Hopkins University School of Medicine in 1988. He is a member of the Howard Hughes Medical Institute and has been elected to the National Academy of Medicine, the National Academy of Sciences, and the American Academy of Arts and Sciences. For 16 years, he directed the Hopkins MD-PhD Program at Johns Hopkins.Robert Siliciano and his wife Janet Siliciano lead a laboratory that is focused in finding a cure for HIV infection. Following the lab’s discovery in 1995 of a latent reservoir for HIV, they demonstrated that latently infected cells persist indefinitely even in patients on prolonged antiretroviral therapy (ART). These studies indicated that eradication of HIV‑1 infection with ART alone would never be possible. The lab is now focused on understanding the in vivo dynamics of this reservoir, specifically the factors that account for the remarkable stability of the reservoir. The lab is also working to identify drugs that will reactivate latent HIV so that it can be targeted by the immune system, and to develop accurate, scalable assays that can be used to evaluate curative interventions. In addition, the lab has studied theoretical aspects of the pharmacodynamics of antiretroviral drugs in an effort to understand the remarkable ability of these drugs to block HIV replication.
AT-527, a double prodrug of a guanosine nucleotide analog, is a potent inhibitor of SARS-CoV-2 in vitro and a promising oral antiviral for treatment of COVID-19
Jean-Pierre Sommadossi is the founder of Atea Pharmaceuticals (NASDAQ: AVIR), where he currently serves as the Chairman & CEO. Jean-Pierre has over 30 years of scientific, operational, strategic and management experience in the biotech industry. Previously Jean-Pierre was the Principal Founder of Idenix Pharmaceuticals, Inc. (NASDAQ: IDIX) and a Co-Founder of Pharmasset, Inc. (NASDAQ: VRUS). Both of these companies were acquired; Idenix by Merck for $3.85 billion in 2014 and Pharmasset by Gilead for $11 billion in 2012. Jean-Pierre held a number of key executive positions at Idenix, including Chairman of the Board of Directors, Executive President and Chief Scientific Officer from 1998 to 2000, and then as Chairman and Chief Executive Officer from 2000 to 2010. During Jean-Pierre’s tenure, Idenix discovered, co-developed and co-launched telbivudine (Tyzeka™/Sebivo®) for the treatment of hepatitis B, and established a major clinical pipeline of antiviral therapeutics for the treatment of hepatitis C and HIV/AIDS. Jean-Pierre is a member of the Harvard Medical School Discovery Council, Chairman, Kezar Life Sciences, Inc. (NASDAQ: KZR), Chairman of PegaOne, Chairman, Panchrest, Inc., and a member of the Board of The BioExec Institute, as well. Prior to his entrepreneurial career, Jean-Pierre was on the faculty of the University of Alabama at Birmingham School of Medicine since March 1985. Jean-Pierre served as a Professor of Pharmacology, Toxicology and Clinical Pharmacology from June 1992 to November 2000. He has authored over 180 peer-reviewed publications and holds more than 60 U.S. patents associated with cancer and antiviral therapeutics. Jean-Pierre holds a PharmD and PhD in Pharmacology from the University of Marseilles, France.
Principles of Hepatitis E virus replication, persistence and antiviral strategies
Prof. Eike Steinmann studied Biology at the Leibniz University Hannover and at the Northeastern University, Boston, USA. He graduated in 2004 at the Institute for Molecular Virology at University Heidelberg in the lab of Prof. Bartenschlager. Afterwards he worked as a postdoctoral fellow and junior group leader in the Department for Experimental Virology of the TWINCORE - Centre for Experimental and Clinical Infection Research. In 2012, Eike habilitated for Experimental Virology at Hannover Medical School and in 2014 he became group leader of the Virus Transmission team at the Institute for Experimental Virology at the TWINCORE - Centre for Experimental and Clinical Infection Research. Eike became extracurricular professor at the Hannover Medical School in 2016 and was then appointed to the Ruhr University Bochum, where he is head of the Department for Molecular & Medical Virology since April 2018.
Towards combination treatments for chronic hepatitis B: A virologist point of view
John Tavis, Ph.D., is a Professor of Molecular Virology at the Saint Louis University School of Medicine and Director of the Saint Louis University Institute for Drug and Biotherapeutic Innovation. He received his doctorate in molecular biology from Penn State University in 1990 and did postdoctoral studies into the molecular virology of Hepatitis B Virus at the University of California – San Francisco. He is the Chairman of the Scientific Advisory Council for the annual International Hepatitis B Virus Meeting, Incoming Chair of the International Coalition to Eliminate HBV (ICE-HBV), and a member of the Scientific and Medical Advisory Board for the Hepatitis B Foundation and Baruch S. Blumberg Institute. He is on the editorial boards of the Journal of Virology and Antiviral Research. He is the recipient of the 2013 Naomi Judd Award for his efforts to control HBV. His longstanding efforts on behalf of the American Cancer Society led to receipt of the Society’s Mission Hero Award in 2018. He has studied the HBV replication mechanism, HBV reverse transcriptase’s metabolism and non-catalytic roles in the cell, and biochemistry of viral reverse transcription since 1992. He has authored approximately 100 scientific papers and is an inventor on 10 awarded or pending patent applications. His current work focuses on the basic biochemistry of the HBV ribonuclease H and developing drugs to suppress HBV replication that target this essential enzyme.
Investigating enterotropic virus infections in human intestinal organoids
Dr. Christiane Wobus is an associate professor in the Department of Microbiology and Immunology at the University of Michigan Medical School in Ann Arbor, MI, USA. In 1997, she received her MS from Michigan State University, East Lansing, MI, USA, and her PhD from the University of Heidelberg, Germany, in 2000. She returned to the USA to perform her postdoctoral work at Washington University in St. Louis, MO, where she co-discovered murine norovirus and her interest in enteric viruses was ignited. In 2007, she joined the University of Michigan as an assistant professor and was promoted to associate professor in 2014. Today her laboratory investigates different aspects of noroviruses and astroviruses, major causes of gastroenteritis worldwide, using a combination of transformed cell culture systems, non-transformed intestinal organoids and mouse models. After the start of the COVID-19 pandemic, she has also applied her expertise to better understand SARS-CoV-2 biology and identify therapeutics. The long-term goal of her research program is to gain a better understanding of enteric viruses and identify conserved features that may lead to the development of effective prevention and control strategies for viral causes of gastroenteritis.
Overview of Moderna COVID-19 Vaccine: Safety, Immunogenicity and Efficacy
Tal Zaks, Chief Medical Officer, oversees clinical development and regulatory affairs across Moderna. Prior to joining Moderna, Dr. Zaks was senior vice president and head of Global Oncology at Sanofi, where he was responsible for all aspects of oncology drug discovery, development and commercialization. Dr. Zaks began his industry career at GlaxoSmithKline in the genetics research group, where he built the oncology translational medicine team and led translational research on lapatinib as well as the in-licensing and clinical development of foretinib. In addition to his industry work, Dr. Zaks is associate professor of medicine at the University of Pennsylvania, and has served as a volunteer physician at the Philadelphia Veterans Administration Medical Center, treating patients with genitourinary cancers. Dr. Zaks received his M.D. and Ph.D. from the Ben Gurion University in Israel and conducted post-doctoral research at the U.S. National Institutes of Health. He completed his clinical training in internal medicine at Temple University Hospital followed by a fellowship in medical oncology at the University of Pennsylvania. Dr. Zaks serves on the Board of Directors of Adaptimmune Therapeutics plc.
Lenacapavir: A first-in-class phase 2/3 HIV capsid inhibitor with potential for twice yearly dosing
Jennifer R. Zhang joined Gilead Sciences as a medicinal chemist in 2003 after working for 5 years at Sugen, Inc. Over the past 17 years, she has worked on multiple programs including the discovery of GS-9669, a non-nucleoside inhibitor of the hepatitis C NS5B RNA polymerase. More recently, she has contributed to HIV projects such as the discovery of the first-in-class HIV capsid inhibitor, lenacapvir. Jennifer received MS and BS degrees in chemistry from Peking University, China.
The International Society for Antiviral Research (ISAR) is an internationally recognized organization for scientists involved in basic, applied, and clinical aspects of antiviral research. The Society main event is the annual International Conference on Antiviral Research (ICAR), a truly interdisciplinary meeting which attracts the interest of chemists, biologists, and clinicians.