Join us on our mission to build better treatments for the current pandemic,
and ensure we are prepared for the next one.
Research Projects
The Center comprises six Projects that are supported by five Cores.
Project 1
Novel CoV Protease Inhibitors
Arnab Chatterjee | Calibr
Gaetano T. Montelione | Rensselaer Polytechnic Institute
Shaun Stauffer | Cleveland Clinic
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Objective 1
Optimization of a once-a-day oral CLpro inhibitor for SARS-CoV-2.
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Objective 2
Identification and Development of novel non-covalent inhibitors of SARS-CoV-2 CLpro.
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Objective 3
Novel approaches to targeting SARS-CoV-2 PLpro.
Project 2
Novel CoV Polymerase Inhibitors
Christopher F. Basler | Icahn School of Medicine at Mount Sinai
Gustavo Palacios | Icahn School of Medicine at Mount Sinai
Matthias Götte | University of Alberta
Christopher Parker | Scripps Research
Ben Cravatt | Scripps Research
Case McNamara | Calibr
Matthew Frieman | University of Maryland School of Medicine
Anil Gupta | Calibr
Objective 1
Identification and development of novel nucleoside inhibitors of SARS-CoV-2 RDRP.
Objective 2
Screening of fragment-based chemical proteomic libraries to identify novel small molecule inhibitors of the SARS-CoV-2 polymerase in native environments.
Objective 3
Evaluate potent hits for pan-coronavirus activity and define the molecular basis for broadspectrum activity.
Project 3
Next-generation Antivirals Against
SARS-CoV-2 Druggable Proteins
Michael Farzan | UF Scripps Biomedical Research
Sumit Chanda | Scripps Research
Suganya Selvarajah | Prosetta Biosciences
John Guatelli | University of California San Diego
Stanley Opella | University of California San Diego
Stuart Lipton | Scripps Research
Hyeryun Choe | Scripps Research
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Objective 1
Nsp13 helicase.
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Objective 2
Nucleocapsid assembly.
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Objective 3
E protein ion channel activity.
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Objective 4
S protein-targeting entry inhibitors.
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Project 4
Antivirals Against Undruggable SARS-CoV-2 Targets
Adolfo García-Sastre | Icahn School of Medicine at Mount Sinai
Sumit Chanda | Scripps Research
Matthew D. Disney | UF Scripps Biomedical Research
Jose Gallego | Catholic University of Valencia
Hong Moulton | Oregon State University
Matthew J. Evans | Icahn School of Medicine at Mount Sinai
Beatriz Fontoura | UT Southwestern
Luis Martinez-Sobrido | Texas Biomedical Research Institute
Christopher Parker | Scripps Research
Ben Cravatt | Scripps Research
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Objective 1
SARS-CoV-2 inhibition by targeting Nsp1.
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Objective 2
SARS-CoV-2 inhibition by targeting RNA sequence.
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Objective 3
SARS-CoV-2 inhibition by targeting RNA structures.
Project 5
Development of Antivirals to Flaviviruses
Sara Cherry | University of Pennsylvania
Sumit Chanda | Scripps Research
Michael S. Diamond | Washington University School of Medicine
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Flaviviruses are a genus of positive, single-stranded, enveloped RNA viruses that are vectored by arthropods and can cause severe illnesses in humans. Flaviviruses including Dengue (DENV), West Nile virus (WNV), Japanese encephalitis (JEV), and Zika (ZIKV) viruses are transmitted by mosquitoes and cause hundreds of millions of infections annually with a range of syndromes including hemorrhagic fever, encephalitis, liver failure, and congenital disease. DENV alone infects an estimated 400 million humans every year that range from asymptomatic infection to severe disease, being the mortality rate of severe dengue shock syndrome over 20%
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Objective 1
Develop pan-anti-flavivirus nucleoside analogs.
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Objective 2
Develop antiviral inhibitors against non-enzymatic targets.
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Objective 3
Lead optimization and in vivo efficacy studies.
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Project 6
Development of Therapeutics for Hemorrhagic Fever Viruses
Juan Carlos de la Torre | Scripps Research
Christopher F. Basler | Icahn School of Medicine at Mount Sinai
Jae Jung | Cleveland Clinic
Robert Davey | Boston University
Gaya Amarasinghe | Washington University School of Medicine
Christopher Parker | Scripps Research
Suganya Selvarajah | Prosetta Biosciences
Sumit Chanda | Scripps Research
Luis Martinez-Sobrido | Texas Biomedical Research Institute
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Ebolaviruses (EBOV) belong to the Filovirus family and are emerging non-segmented, negative-sense RNA viruses that cause severe and often fatal disease in humans. Since the Ebola disease causing virus was first identified in 1976, the virus has emerged periodically across several African countries. Following the largest outbreak in West Africa during 2014-2016 with an average fatality rate of 50%, the virus has re-emerged in the Republic of the Congo and Guinea where it continues causing severe disease.
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Objective 1
Development of novel inhibitors of EBOV replication.
Objective 2
Discovery and development of SFTSV and LASV L polymerase
inhibitors.
Objective 3
Discovery and development of LASV and EBOV NC formation inhibitors.
Objective 4
Discovery and development of inhibitors of viral endonuclease (EndoN) and Cap-binding (CB) activity required for cap-snatching
mediated transcription of SFTSV and LASV
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Core A
High-throughput Screening Core
Kristen Johnson | Calibr
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Objective 1
Arrangement, plating, supplementation and coordination of high value antiviral and chemically diverse, small molecule libraries
for high throughput screening, hit follow-up and medicinal
chemistry campaigns
Objective 2
Development and high throughput screening of small molecule libraries in direct-acting and cellbased antiviral assays.
Objective 3
Execution of target-based and cell-based assays to enable structural activity relationship (SAR) studies, and subsequent optimization
of small molecule lead candidates during the Hit-to-Lead and
Lead Optimization stages.
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Core B
Medicinal Chemistry Core
Anil Gupta | Calibr
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Objective 1
Perform unified HTS triage i.e. enable the selections of hits based on potency and diverse chemotype (working in conjunction with HTS Core A).
Objective 2
Perform medicinal chemistry on hit and lead compounds to enable SAR for all projects.
Objective 3
Incorporate the preliminary in vitro ADME/T properties of hit and early lead compounds and then select specific lead compounds
for Lead Optimization to determine preclinical candidates (working in conjunction with ADME/Formulation Core C).
Objective 4
Plan and perform GMP process development and manufacturing of lead candidates.
Core C
Pharmacology & Formulation Core
Sean Joseph | Calibr
Victor Chi | Calibr
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Objective 1
Measure the ADMET properties of project compounds in vitro to guide medicinal chemistry to preclinical candidate selection.
Objective 2
Assess the in vivo pharmacokinetics and drug metabolism data for project compounds in rodents and non-rodents for in vivo
efficacy and safety studies using optimized formulations to pre-clinical candidate selection.
Objective 3
Execute in vivo toxicology studies for advanced compounds including single and repeat dose tolerability, non-GLP dose-range
finding toxicity and in IND-enabling GLP toxicology studies and scale up of GMP drug product.
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Core D
Organoid & Animal Model Core
John Teijaro | Scripps Research
Matthew Frieman | University of Maryland School of Medicine
Jae Jung | Cleveland Clinic
Thomas Rogers | University of California San Diego
Kanta Subbarao | University of Melbourne
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Objective 1
Assess selected candidate anti-Coronavirus compounds in organoid and animal models.
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Objective 2
Assess selected candidate compounds against hemorrhagic fever viruses in animal models.
Core E
Structural Biology and Computational Modeling Core
Ian Wilson | Scripps Research
Andrew Ward | Scripps Research
Stefano Forli | Scripps Research
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Objective 1
Production, biophysical, and biochemical characterization of target proteins.
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Objective 2
High-resolution structures of protein targets and complexes by x-ray crystallography.
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Objective 3
High-resolution structures of protein targets and complexes by cryo-electron microscopy.
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Objective 4
In silico structure-based modeling for compound identification and optimization.
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Industry & Foundation Partners
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Prosetta Biosciences
HitGen
Schrödinger
Johnson & Johnson
Intrepid Alliance
Gilead
Atomwise
Bill & Melinda Gates Foundation
Wellcome Trust