EXCELLENCE IN ANTIVIRAL
The UC-NL ATTACK Consortium Combines the Antiviral Drug Discovery Potential of
Six UC Campuses and Two National Labs
B U I L D I N G A D R U G D I S C O V E R Y
N E T W O R K FOR PATHOGENS OF PANDEMIC CONCERN
The University of California-National Labs ATTACK Consortium is a cross-institutional initiative aimed at building an antiviral drug discovery community that actively promotes research and translates discoveries through industry partnerships.
Our overall goal is to not be caught off-guard by viral pandemics ever again.
To meet this goal our University of California-National Laboratories Antiviral Treatments Targeting All Coronaviruses and Key RNA viruses (UC-NL ATTACK) Consortium has developed a fully integrated, multidisciplinary, cutting-edge drug discovery and validation program. Our Consortium has a robust pipeline from validated identification of novel viral targets, to discovery and optimization of lead chemical series, to late-stage preclinical development and IND-enabling profiling of specific drug candidates. Our first antiviral targets will be against coronaviruses, Enterovirus D68, dengue virus and Nipah virus. Other key viruses will be tackled based on urgent need, scientific progress and opportunity.
To be smart and efficient, our Consortium seamlessly integrates our units across our 8 institutions and 13, highly engaged, industry partners across the drug development continuum. These connections provide access to unique, large high-quality chemical libraries (~1,280,000 compounds) for direct acting antiviral hit identification and novel, propriety technology to overcome specific antiviral development hurdles (e.g., structure-based design, endosome escape, inhalation delivery, development of viral resistance). These partnerships also bring in pharmaceutical-level expertise in medicinal chemistry, regulatory and pharmacology. Such breadth of expertise and technology is practically impossible in a single company or single academic institution.
To be prepared, we are also training the next generation of antiviral therapies. Thus, we have a training pipeline to complement our drug delivery pipeline. Our training will provide the skills and hands-on tools needed to develop the next generation of antiviral researchers. Understanding that diversity is important to our overall success, we have incorporated justice, equity, diversity and inclusion (JEDI) principles within our training pipeline and throughout our Consortium
E X E C U T I V E
C O M M I T T E E
Meet the Institutional and Project Leads
The UC-NL ATTACK Consortium is governed by a diverse group of experts in virology, drug discovery and development that represent the institutions and individual teams.
Davey Smith is an infectious disease specialist and translational research virologist, and has published over 300 scientific publications in these areas. In 2010, Dr. Smith was named HIV Researcher of the Year by the HIV Medical Association, and in 2016, he became the co-director and principal investigator of the San Diego Center for AIDS Research (CFAR). Since the outbreak of SARS-CoV-2 in 2019, Dr. Smith has been engaged in the international effort to find safe and effective treatments. In particular, he is the international protocol chair for the ACTIV-2 treatment study, which is a part of the US government’s response to COVID-19 to find effective therapies for persons with early COVID-19.
Mike Jung received his Bachelor of Arts in 1969 from Rice University, doing research with Richard Turner, and then his PhD in 1973 from Columbia, where he worked with Gilbert Stork. After a one-year NATO postdoctoral fellowship with Albert Eschenmoser at the ETH in Zurich, he joined the faculty at UCLA in 1974. He has risen through the ranks at UCLA and is now a Distinguished Professor of Chemistry. He has served as a reviewer of proposals for various organizations, e.g., NSF, PRF, NIH Medicinal Chemistry Study Section, Research Corporation and others. He is on the Scientific Advisory Boards of several pharmaceutical firms and consults currently for more than 20 industrial laboratories in both the biotech and big pharma settings. Professor Jung is an authority on synthetic organic and medicinal chemistry and has more than 25 patents arising from both his consulting activities and his own research and brought several compounds to the clinic. At this point in time, Professor Jung is workin on antiviral compounds such as oxetanocin A and its analogues, both the carbocyclic ones, e.g., cyclobut-A and G, and the C-oxetanocins (related to oxetanocin H), methylene-expanded oxetanocins, several modified N-nucleosides (2',3'-dideoxycytidine and analogues, AZT, d4T and their analogues, l-3-TC), carbovir, and the cyclophellitols. He is also investigating new methods for the preparation of l-carbohydrates and their corresponding modified nucleosides, e.g., l-5-F ddC, which have shown strong antiviral activity. As possible reagents for antisense oligonucleotide therapy, we are preparing both l-DNA and l-RNA. Finally we are preparing several isonucleosides and 4'-substituted 2'-deoxynucleosides as potential antiviral agents.
Brigitte Gomperts is Professor of Pediatrics and Pulmonary Medicine at UCLA. Her lab has developed human models of airway viral infection for drug discovery. She is a physician-scientist who has been a faculty member at UCLA for over 18 years. She is also Co-Director of the Jonsson Comprehensive Cancer Center Cancer Stem Cell Biology Program and Vice Chief of Research for Pediatric Hematology-Oncology. As a physician-scientist, her lab is particularly interested in translational research that will result in new therapies for lung diseases.
Robert Damoiseaux’s main interests are in Drug Discovery and Development. He has extensively published on the development of novel assay technology platforms, High Throughput Screening, High Content Screening and nanotechnology. He is the Director of the Molecular Shared Screening Resources (MSSR) at the California NanoSystems Institute of UCLA and Professor in the Department of Molecular and Medical Pharmacology and is inventor on numerous patents with several compounds originating in his laboratory in clinical trials.
My laboratory focuses on understanding the pathogenic mechanisms of viruses such as SARS-CoV-2 and also Flaviviridae viruses like Hepatitis C Virus, Zika Virus and Dengue Virus. Currently, I am working on potential small molecule drugs for SARS-CoV-2 as well as vaccine or treatment available against ZIKV. We have developed a reverse genetics system to engineer attenuating mutations in the Zika viral genome and animal models to test the safety and immunological profiles of these engineered vaccine candidates. For modeling congenital e.g. ZIKV eye disease, we are utilizing human pluripotent stem cells derived ocular progenitor cells and 3D optic cup organoids. In these human cell-based systems, we have observed differential activation of signaling pathways and long non-codling RNAs (lncRNAs) by various Zika viral pathotypes. We are evaluating the genetic and molecular basis of these specific cellular perturbations, which can allow for understanding the basic biology of eye development and identifying novel therapeutic interventions.
David Eisenberg is a Professor of Chemistry and Biochemistry and of Biological Chemistry at the University of California, Los Angeles, and Director of the UCLA-DOE Institute for Genomics and Proteomics. He received his undergraduate degree in biochemical sciences from Harvard College and his D.Phil. degree in theoretical chemistry from Oxford University. His postdoctoral research was on ice and water with Walter Kauzmann at Princeton and in protein crystallography with Richard Dickerson. Dr. Eisenberg is a member of the National Academy of Sciences and the Institute of Medicine. He is a recipient of the 2004 UCLA Seaborg Medal, the 2005 Harvard Westheimer Medal, and the 2008 Emily Gray Award from the Biophysical Society.
Dr. Coffey has 21 years of experience studying the transmission dynamics, evolution, and pathogenesis of mosquito-borne viruses. Research in her laboratory, which is based in the School of Veterinary Medicine, focuses on viral genetic mechanisms of emergence that alter virus-host interactions, with a goal of finding ways to interrupt transmission to reduce human disease.
Dr. McKerrow received his PhD in Biology from the University of California, San Diego and MD from the State University of New York. He has published more than 220 peer-reviewed manuscripts and currently leads a consortium of academic and industry scientists dedicated to the discovery and development of new drugs for neglected tropical diseases. This consortium, the Center for Discovery and Innovation in Parasitic Diseases, is focused on drug discovery and development through Phase I clinical trials. The Center includes expertise in structure-based drug design, high-throughput screening and animal models of tropical diseases. Among his accomplishments, Dr. McKerrow has developed a drug for Chagas’ disease through a successful pre-IND meeting with the FDA.
Dr. Pellecchia is a Professor of Biomedical Sciences at the School of Medicine of the University of California Riverside (UCR) and is the founding Director of the Center for Molecular and Translational Medicine at UCR. His research laboratory focuses on the design of novel pharmacological tools and therapeutics in oncology, neurodegeneration, and other disease areas.
Steven Dowdy, PhD - University of California, San Diego
Over the last 27 years, Dr. Dowdy’s lab has pioneered delivery of macromolecular therapeutics and for the last 17 years on the molecular details of delivery of RNA therapeutics across the endosomal lipid bilayer. His lab was the first to synthesize bioreversible, charge neutralizing phosphotriester backbone RNAi prodrug triggers that increase metabolic stability, pharmacokinetics and enhance endosomal escape. Currently, his lab is synthesizing novel biomimetic endosomal escape domains to overcome the rate-limiting delivery step of endosomal entrapment. Dr. Dowdy will lead development of anti-viral siRNAs and enhancement of endosomal escape.
Dr. Dandekar's Under is the chair of the Department of Medical Microbiology and Immunology at UCD. Her research program is focused on the molecular pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections with special emphasis on gastrointestinal mucosal lymphoid tissue (GALT) as a major target organ of the viral infection and as a viral reservoir. Dr. Dandekar's research demonstrates for the first time that gastrointestinal mucosal tissue is an early target organ of HIV and an early site for viral replication and severe CD4+ T cell depletion. She has successfully integrated basic and clinical studies to determine the pathogenic mechanisms of mucosal HIV infection. Dr. Dandekar's other research focus is in understanding enteropathogenic mechanisms of HIV and SIV pathogenesis. She has been responsible for developing an SIV enteropathogenic model for the studies of HIV-associated enteropathy.
My research uses cutting-edge, multi-scale, in silico simulations to tackle problems in biology. A wide range of computational biology and machine learning methods that employ LLNL’s high-performance computing resources are used to accelerate the design and development of new therapies.
Brian Paegel is a professor in Departments of Pharmaceutical Sciences, Chemistry, and Biomedical Engineering at UC Irvine. He is an expert in DNA-encoded library technology, miniaturization, automation, and assay development.
Dr. Momper’s research focuses on the application of quantitative pharmacology approaches to optimize the development and clinical use of drugs. He was previously the Commissioner’s Fellow in the Office of Clinical Pharmacology at the U.S. Food and Drug Administration. Current research directions include evaluation of potential therapies for HIV infection in infants and pregnant women and the use of model-based methods to support scientific decision making in drug development. Dr. Momper directs the Translational Pharmacology and Bioanalysis Laboratory at UC San Diego concentrated on novel mass spectrometry-based analytical methods, in vitro ADME assays, and pre-clinical and clinical pharmacokinetic studies.
David Avery has 20+ years of administrative and grants management experience, specializing in large, complex, multi-institutional research programs.