Viral Protease Targets

Don Francis

James Mckerrow Ph.D, M.D

Distinguished Professor & Dean

Skaggs School of Pharmacy and Pharmaceutical Sciences

Associate Vice Chancellor for Health Sciences

UC San Diego

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. In addition, Dr. McKerrow has shown that a repurposed anti-parasitic drug can successfully treat SARS-CoV-2 in non-human primates and this drug has recently successfully completed Phase I trials. 


Drug discovery and development with a particular focus on IND enabling studies for cysteine protease inhibitors. More than 20-years of leadership experience as Director of Center for Discovery and Innovation in Parasitic Diseases and Dean of Skaggs School of Pharmacy and Pharmaceutical Sciences. 
 

123-456-7890

  • Facebook
  • Twitter
  • LinkedIn
Wooden Hut

Ashley Jones

Larissa Podust, Ph.D,

Professor,

Skaggs School of Pharmacy,

UC San Diego


My laboratory specializes in the structure-based drug discovery against infectious diseases caused by a variety of human pathogens. We use x-ray crystallography, enzymology and biochemistry methods to establish mechanisms of drug action, identify novel chemotherapeutic targets and guide hit-to-lead optimization to support discovery of drug candidates for the treatment of the infectious diseases. During my career as a biochemist and structural biologist I have contributed to PDB, the public database of protein structures, >100 crystal structures of diverse enzymes (proteases, monooxygenases, reductases), electron transporters, and transcription factors derived from different organisms, including human pathogens of Global Health importance. The x-ray structures determined in my laboratory will contribute in structure-based drug discovery efforts of ATTACK Consortium targeting viral drug targets and leading to novel patentable chemical matter

Larissa-Podust-68.jpg

Tess Brown

Anthony O’Donoghue, Ph.D.
Associate Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences
UC San Diego

Dr. O’Donoghue obtained his Ph.D from National University of Ireland, Galway and was a postdoctoral fellow at the University of California, San Francisco.  He specializes in the discovery and characterization of proteases in infectious organisms, cancerous tissues, immune cells and human biofluids.  Following in depth characterization of the target proteases, he develops potent and selective inhibitors to inactivate these enzymes or fluorogenic substrates to monitor their catalytic activity. Dr. O’Donoghue has published more than 70 papers that are focused on proteases and protease inhibitors. More recently he has been focused of screening inhibitors of viral proteases and in utilizing viral proteases as rapid diagnostic agents. He has collaborated extensively with RP5 Lead, Mckerrow and co-investigators Gerwick and Abagyan to discover antiviral protease inhibitors. Dr. O’Donoghue is currently the President of the International Proteolysis Society (2019 to 2023).

Dr. O'Donoghue bring his expertise in recombinant protease expression, assay development, high-throughput enzyme assays and inhibition kinetics to ATTACK.  

Anthony O'Donoghue_headshot.jpg

William Gerwick, Ph.D.
Distinguished Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences
Scripps Institution of Oceanography

UC San Diego

Lisa Rose

Dr. William Gerwick is a Distinguished Professor of Oceanography and Pharmaceutical Sciences at UC San Diego.  He received his training with a BS degree from UC Davis and PhD from UC San Diego, postdoctoral work at the U Connecticut School of Pharmacy, and was a professor of Pharmaceutical Sciences in the College of Pharmacy at Oregon State University for 21 years before joining at UC San Diego in 2005.  His laboratory has explored multiple dimensions of marine natural products science, including bioactive compound discovery and characterization, method development in natural products including NMR spectroscopy and applications of Artificial Intelligence, genetics and biosynthesis of natural products, and chemical synthesis of natural products and their analogs in the pursuit of drug development. He has trained more than 100 PhD and postdoctoral students, published over 500 peer reviewed papers, and holds numerous patents.

The Gerwick laboratory brings to the ATTACK program an extensive library of marine natural product compounds, impure fractions and crude extracts that have been obtained from diverse marine algae and cyanobacteria collected around the globe over the past 40 years.  These collections have been extraordinarily rich in yielding structurally diverse and biologically active natural products, resulting in the productivity of this laboratory over many years.  In this project, the Gerwick laboratory will mine this unique collection of bioactive compounds for antiviral compounds, and then has the expertise to isolate and structurally define novel compounds from these as well as pursue select leads through creation of analogs by biosynthetic and semi-synthetic methodologies.
 

Gerwick.jpg
Jair-NCLAM.jpg

Jair L. Siqueira-Neto, Ph.D.
Associate Adjunct Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences

UC San Diego

Dr. Siqueira-Neto has a PhD in Microbiology, Genetics & Molecular Biology from UNICAMP, ranked #1 in Brazil. He worked for 5 years at the renowned Institute Pasteur Korea developing the first cell-based high-throughput screening using intracellular kinetoplastid parasites, having screened libraries for Pfizer, Merck, AstraZeneca, and GlaxoSmithKline among others. He is currently an Associate Professor at the Skaggs School of Pharmacy & Pharmaceutical Sciences and UCSD Screening Core director at UC San Diego. He has also established cell-based screening models against Zika virus and SARS-CoV-2.

 

Dr. Siqueira-Neto is an expert in drug discovery and development, with compounds in clinical stage of development. He has an extensive experience with cell-based models of infectious diseases including RNA viruses such as flaviviruses and coronaviruses. His laboratory has also focused on proteases as a therapeutic target against infectious organisms with a good track record of publications and scientific contributions in this area.

Lisa Rose

Ruben Abagyan, Ph.D.

Professor

Skaggs School of Pharmacy and Pharmaceutical Sciences

UC San Diego

Dr. Abagyan received his Ph.D. degree in molecular physics at MPTI and MSU. At EMBL in Heidelberg, he developed internal coordinate mechanics and structural docking approach (ICM) for modeling and docking. He is an expert in computer-aided drug design, screening and properties.  He founded Molsoft LLC, received his tenure at New York University and Courant Institute of Mathematics, continued at Novartis Functional Genomics Institute as a Director of Computational Chemistry, the Scripps Research Institute and UCSD in La Jolla as a professor. He has over 330 publications and 37,700 citations, H-index of 93, several awards, including the Princess Diana Award. 

 

Dr Abagyan has discovered Mpro/PLpro inhibitors and will use his expertise in structure and AI-based drug discovery to identify compounds targeting viral proteases using large scale screens of both covalent and non-covalent lead candidates. In addition he will perform multi-parameter optimization, and evaluate drug-resistant mutations.

Ruben.png
Clemens.jpg

Lisa Rose

Daniel L. Clemens, M.D., Ph.D.
Adjunct Professor
UCLA

Daniel Clemens is Adjunct Professor in the Division of Infectious Diseases, Department of Medicine at UCLA.  He received his MD-PhD (Biochemistry) degrees at Vanderbilt University, residency training in Internal Medicine at Johns Hopkins Hospital and fellowship training in Infectious Diseases at UCLA.  He has extensive experience in the study of the virulence mechanisms and host-pathogen interactions of BSL2 and BSL3 organisms, including Legionella pneumophila, Mycobacterium tuberculosis, and Francisella tularensis, and development of novel therapeutics against these infectious organisms. Key accomplishments include the first comprehensive proteomic study of the Mycobacterium bovis BCG phagosome, the discovery that M. tuberculosis inhibits phagosomal maturation, identification of a novel uptake pathway (“looping phagocytosis”) and unique intracellular lifestyle of F. tularensis, purification of the Francisella Type 6 Secretion System and determination of the composition and atomic structure of its sheath and spike, development of nanotherapeutics for treatment of tularemia and tuberculosis, and identification via in vitro and in vivo parabolic response surface mapping of highly effective combinatorial drug regimens for rapid treatment of tuberculosis.  Working with Dr. Bai-Yu Lee in the laboratory of Dr. Marcus Horwitz, he has developed high throughput FRET based screening assays for identification of inhibitors of the SARS-CoV2 Mpro and PLpro cysteine proteases and SDS-PAGE based orthogonal assays for confirmation of hit compounds, and he will continue to use these robust tools to identify promising compounds for drug development in the ATTACK Consortium.  

Fenical photo 2021.jpg

Lisa Rose

William Fenical, Ph.D
Distinguished Professor
Chemical Biology and Pharmaceutical Science
Center for Marine Biotechnology and Biomedicine
Scripps Institution of Oceanography
UC San Diego

I am a trained organic and bioorganic chemist who has been at UCSD since 1973.  I was an early founder of the field of marine natural products drug discovery and paved the way to isolate and cultivate marine bacterial for biomedical discovery.  My work has resulted in two cancer drugs both of which are in late phase III cancer clinical trials for NSCLC and glioblastoma, as well as a new and potent anti-inflammatory agent.  I have produced more than 500 publications in the field of marine natural products drug discover

 

Over the past 25 years I have developed a large collection of chemically-prolific marine bacteria.  Over 17,000 strains have been cultured and a large compound library of over 30,000 samples has been established.  I intend to dedicate this library for screening in the ATTACK Consortium and to work with the screening group(s) to discover, describe and produce new antivirals in sufficient scale to allow animal studies and to facilitate preclinical drug development

Photo Marcus A. Horwitz 7Final High II.jpg

Marcus A. Horwitz, M.D.
Distinguished Professor of Medicine and 
    Microbiology, Immunology & Molecular Genetics
UCLA

Dr. Horwitz received his B.A. (Physics) from Cornell University and M.D. from Columbia University; trained in Internal Medicine and Infectious Diseases at Albert Einstein College of Medicine; served as an Epidemic Intelligence Service Officer at CDC; and did post-doctoral training and served on the faculty of The Rockefeller University before joining the faculty of UCLA as Professor and Chief of Infectious Diseases.  Dr. Horwitz is a fellow in the Infectious Diseases Society of America and a member of the American Society for Clinical Investigation, and his awards include the Oswald Avery (formerly Squibb) Award from the Infectious Diseases Society of America and election to Fellowship in the American Association for the Advancement of Science.  He has served as Chairman of the Scientific Advisory Board of the American Leprosy Foundation; on the Tuberculosis Panel of the U.S.-Japan Cooperative Medical Sciences Program; on the Board of Trustees of the Trudeau Institute; as an Advisor to the World Health Organization Global Forum on TB Vaccines Research and Development; on the Cornell University Life Sciences Advisory Board; and on the Editorial Boards of Infection and Immunity and The Journal of Clinical Investigation, a journal for which he also served as Guest Editor. His research has focused on the immunobiology of the agents of Legionnaires' disease, leprosy, tuberculosis, and tularemia and development of vaccines, nanotherapeutics, and drugs against these pathogens.   
   In addition to the development of numerous vaccines including rBCG30, the first vaccine against TB more potent than BCG and the first recombinant BCG vaccine to enter clinical trials, where it has demonstrated safety and immunogenicity, Dr. Horwitz brings to the ATTACK Consortium expertise in drug development including a) preclinical development of exochelins for treatment of diverse disease entities including ischemia/reperfusion injury associated with acute myocardial infarction and organ transplantation; restenosis following coronary artery angioplasty; and iron-overload; b) development of the thiol antioxidant bucillamine for treatment of oxidative injury in organ transplantation, which has completed a successful Phase 1 human study; and identification via artificial intelligence of novel highly synergistic ultra-short course TB drug regimens including universal regimens to markedly shorten treatment duration of both drug-sensitive and drug-resistant TB and now in clinical trials.  Dr. Horwitz with his laboratory colleagues has 25 issued U.S. Patents (and accompanying foreign patents) on technologies developed in his laboratory for clinical applications.  In preliminary studies, Dr. Horwitz’s group has identified novel compounds that inhibit SARS-CoV-2 proteases, which are essential for viral replication and hence potentially powerful therapeutics.

Lisa Rose

Bai-Yu Lee, Ph.D.
Project Scientist
UCLA

Bai-Yu Lee is Project Scientist in the Department of Medicine at UCLA.  She received her Ph.D. degree from Colorado State University in Microbiology and Immunology. Her main research interests focus on identification and characterization of microbial virulence factors that play a role in host-pathogen interaction.  Dr. Lee works in Professor Marcus A. Horwitz’s laboratory and collaborates with Daniel Clemens, M.D., Ph.D. on several research projects.  Major accomplishments include determination of the composition and structure of the Type VI Secretion System of Francisella tularensis, development of a novel inducible GFP expression system for assessing the metabolic activity of Mycobacterium tuberculosis and discovery that metabolic activity correlates with this bacterium’s capacity to inhibit phagosome maturation and acidification, the first comprehensive characterization of the BCG phagosome proteome, development of nanotherapeutic platforms for diagnosis and treatment of tularemia, identification via an artificial intelligence-enabled approach of ultra-short course drug regimens for treating drug-sensitive and drug-resistant tuberculosis, and development of nanotherapeutics for improved treatment of tuberculosis.  Dr. Lee has extensive expertise in molecular engineering of microbial pathogens and recombinant expression of proteins in prokaryotic and mammalian cells.  She expressed active SARS-CoV2 Mpro and PLpro in E. coli for use in high throughput screening.  She developed an orthogonal assay for hit compounds by engineering chimeric proteins containing duel epitope tags joined by a cleavage site of the SARS CoV2 proteases.  She has screened over 16,500 small molecule library compounds with Dr. Clemens at the UCLA Molecular Screening Shared Resource core facility and has identified several promising hit compounds.

BYL.JPG