Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=-program_officials
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_officials", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=-program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-program_officials" }, "data": [ { "type": "Grant", "id": "7733", "attributes": { "award_id": "1U54CA260517-01", "title": "Admin Core", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2020-09-23", "end_date": "2022-08-31", "award_amount": 268355, "principal_investigator": { "id": 23528, "first_name": "Scott Dexter", "last_name": "Boyd", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "ADMINISTRATIVE AND DATA ANALYSIS CORE: SUMMARY The Administrative and Data Analysis Core of the Stanford U54 SARS-CoV-2 Serological Sciences Center of Excellence will be responsible for providing overall management, data coordination, and oversight for the Center. The Core will establish and maintain the administrative structure and functions of the U54 Center to facilitate communications among investigators to promote their productive collaboration, and among all Center investigators and staff to coordinate efforts, identify and resolve problems, and establish a strong collaborative environment to achieve the aims of the U54 to combine a deep mechanistic analysis of the adaptive immune responses of COVID-19 patients, with a focus on studying underrepresented and at-risk patient populations, to determine the factors that result in effective and durable immunity to SARS-CoV-2 infection. This Core will also contribute to integrated data analysis of the results from all Projects and the Clinical and Virology Core, in support of the Center’s research goals.", "keywords": [ "2019-nCoV", "Achievement", "Address", "Biometry", "COVID-19", "Clinical", "Clinical Virology", "Collaborations", "Communication", "Communities", "Data", "Data Analyses", "Disease", "Ensure", "Goals", "Immunity", "Infection", "Mentors", "Patient-Focused Outcomes", "Patients", "Reporting", "Research", "Research Personnel", "Resources", "Risk", "Science", "Scientist", "Secure", "Serological", "Structure", "Teleconferences", "Time", "Training", "Translations", "adaptive immune response", "collaborative environment", "data management", "data warehouse", "database of Genotypes and Phenotypes", "insight", "medically underserved population", "meetings", "member", "novel diagnostics", "novel therapeutics", "organizational structure", "patient population" ], "approved": true } }, { "type": "Grant", "id": "7734", "attributes": { "award_id": "1U54CA260517-01", "title": "Project 2: B Cells", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2020-09-23", "end_date": "2022-08-31", "award_amount": 939232, "principal_investigator": { "id": 23528, "first_name": "Scott Dexter", "last_name": "Boyd", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT 2: SUMMARY The B cell and plasma cell populations that give rise to serum and mucosal antibodies will ultimately determine the effectiveness and duration of an individual’s humoral immune response to SARS-CoV-2 infection. We will use several mutually-supporting strategies to analyze these cells in the Boyd lab: single B cell phenotyping, B cell receptor (BCR) deep sequencing and determination of antigen specificity with DNA-barcoded antigen tetramers; bulk B cell immunoglobulin gene repertoire sequencing; and monoclonal antibody production from antigen-specific B cells. In complementary strategy, the Jardetzky lab will make use of yeast display libraries of patient-derived single-chain antibody variable fragments (ScFv) enriched for native heavy-light chain pairing to determine the antigen specificity of hundreds to thousands of antigen-specific clones per patient. In longitudinal peripheral blood samples and nasal biopsy samples we will thoroughly characterize antigen-specific B cell clones in patient responses to SARS-CoV-2. We hypothesize that with these data we will be able to determine which features of B cell clonal responses to SARS-CoV-2 are associated with differences in COVID-19 disease severity and differences between populations groups stratified by age, sex, ethnicity and pre-existing conditions, or dysregulated immunity in the context of checkpoint blockade treatment. We further hypothesize that analysis of memory B cell populations together with serological responses may predict which individuals will have longer-lasting humoral protection against reexposure to SARS-CoV-2. Finally, we will evaluate the B cell responses stimulated by natural infection compared to vaccination, beginning with the Covaxx peptide- based vaccine cohort, but with the expectation that additional vaccines will be approved for use during the period of this project funding. In addition to studying aspects of the B cell responses that differ among these clinical scenarios, we will search for features such as “convergent” virus-specific BCRs of highly similar sequences shared between different individuals that may have prognostic value, for example by revealing that an individual has a potent neutralizing antibody response to SARS-CoV-2. Our Aims are the following: Specific Aim 1: Analyze B cell responses in acute COVID-19 disease. Specific Aim 2: Evaluate the formation of B cell memory to SARS-CoV-2. Specific Aim 3: Analyze mucosal B cell and plasma cell responses to SARS-CoV-2 compared to responses of B cells in the blood.", "keywords": [ "2019-nCoV", "Acute", "Affinity", "Age", "Antibodies", "Antibody Response", "Antibody Specificity", "Antigens", "B-Cell Activation", "B-Lymphocyte Subsets", "B-Lymphocytes", "Bar Codes", "Biological Assay", "Biopsy", "Biopsy Specimen", "Blood", "Blood specimen", "COVID-19", "Cell Differentiation process", "Cells", "Clinical", "Clinical Data", "Clinical Virology", "Clonal Evolution", "Clonal Expansion", "Clone Cells", "Communities", "DNA", "Data", "Data Analyses", "Databases", "Disease", "Effectiveness", "Epitopes", "Ethnic Origin", "Frequencies", "Funding", "Immune response", "Immunity", "Immunofluorescence Microscopy", "Immunoglobulin Genes", "Immunoglobulin Somatic Hypermutation", "Immunoglobulin-Secreting Cells", "Immunologic Receptors", "Individual", "Infection", "Joints", "Libraries", "Light", "Link", "Measures", "Memory B-Lymphocyte", "Monoclonal Antibodies", "Mucous Membrane", "Mutate", "Nose", "Patients", "Phenotype", "Plasma Cells", "Plasmablast", "Population", "Population Group", "Receptors Antigen B-Cell", "Resources", "Sampling", "Serologic tests", "Serological", "Serum", "Severity of illness", "Site", "Sorting - Cell Movement", "Specificity", "Specimen", "Structure", "Structure of mucous membrane of nose", "T cell response", "T-Lymphocyte", "TFRC gene", "Time", "Vaccination", "Vaccines", "Viral Antigens", "Virus", "Work", "Yeasts", "base", "cohort", "deep sequencing", "design", "expectation", "follow-up", "immune checkpoint blockade", "improved", "interest", "long term memory", "monoclonal antibody production", "neutralizing antibody", "patient response", "peptide based vaccine", "peripheral blood", "prognostic value", "response", "sex", "synergism", "transcriptome", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "7736", "attributes": { "award_id": "1ZIAAI001280-01", "title": "Pathogenesis of SARSCov2 infection", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 55722, "principal_investigator": { "id": 23532, "first_name": "Jason", "last_name": "Brenchley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe SARSCov2 disease occurs, predominantly, in humans with one of several preexisting conditions including cardiovascular disease, advanced age, obesity, and diabetes. These underlying conditions tend to have inflammation in common. Indeed, dexamethasone treatment is showing utility in COVID19. While the actual mechanisms underlying severe COVID19 are unclear increased coagulopathy seems to be common. Moreover, many individuals have evidence of GI tract involvement in their SARSCov2 infection with diarrhea and viral RNA being present in fecal samples. Individuals with high granulocyte to lymphocyte ratios also tend to be more common among groups with severe disease. We hypothesize the GI tract involvement of SARSCov2 infection leads to translocation of microbial products from the lumen of the GI tract into circulation and these lead to inflammation and coagulopathy. We aim to test the hypothesis that microbial translocation contributes to inflammation in SARSCov2 infection. We also aim to artificially elevate the granulocyte to lymphocyte ratio hypothesizing that this will exacerbate SARSCov2 disease. Finally, we aim to determine how, or if, preexisting immunity to common coronavirus (HKU1) influences subsequent SARSCov2 infection. These studies will involve longitudinal analysis of experimentally SARSCov2-infected Asian macaques. We will assess microbial translocation and the composition of the microbiome in animals and we will experimentally elevate the granulocyte to lymphocyte ratio with granulocyte stimulating factor prior to SARSCov2 infection. Finally, we will follow animals who had previously been experimentally infected with HKU1 and subsequently challenged with SARSCov2.", "keywords": [ "Animals", "Asians", "Benign", "Blood Circulation", "Blood Coagulation Disorders", "COVID-19", "Cardiovascular Diseases", "Cessation of life", "Coronavirus", "Dexamethasone", "Diabetes Mellitus", "Diarrhea", "Disease", "Disease Progression", "Elderly", "Gastrointestinal tract structure", "Goals", "Human", "Immunity", "Incidence", "Individual", "Infection", "Inflammation", "Lead", "Lymphocyte", "Macaca", "Obesity", "Pathogenesis", "Risk Factors", "Sampling", "Testing", "Work", "experimental analysis", "granulocyte", "longitudinal analysis", "microbial", "microbiome composition", "neutrophil", "nonhuman primate", "viral RNA" ], "approved": true } }, { "type": "Grant", "id": "7737", "attributes": { "award_id": "1ZIAHL001027-38", "title": "Three-dimensional Structures Of Biological Macromolecules", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 359079, "principal_investigator": { "id": 23533, "first_name": "Bernard R", "last_name": "Brooks", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1602, "ror": "", "name": "NATIONAL HEART, LUNG, AND BLOOD INSTITUTE", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1602, "ror": "", "name": "NATIONAL HEART, LUNG, AND BLOOD INSTITUTE", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true }, "abstract": "Traditional molecular modeling is performed at atomic resolution, which relies on X-ray and NMR experiments to provide structural information. When dealing with biomolecular assemblies of millions of atoms, atomic description of molecular objects becomes very computational inefficient. We developed a method that uses map objects for molecular modeling to efficiently derive structural information from experimental maps, as well as conveniently manipulate map objects, perform conformational search directly using map objects. This development work has been implemented into CHARMM as the EMAP module. This implementation enables CHARMM to manipulate map objects, including map input, output, comparison, docking, etc. Protein-protein docking using map objects Protein-protein docking is a molecular modeling strategy to predict biomolecular complexes and assemblies. Traditional protein-protein docking is performed at atomic resolution, which relies on X-ray and NMR experiments to provide structural information. When deal with biomolecular assemblies of millions of atoms, atomic description of molecular objects becomes very computational inefficient. This article describes a development work that introduces map objects to molecular modeling studies to efficiently derive complex structures through map-map conformational search. This method has been implemented into CHARMM as the EMAP command and into AMBER in its SANDER program. This development enables molecular modeling and simulation to manipulate map objects, including map input, output, comparison, docking, etc. Through map objects, users can efficiently construct complex structures through protein-protein docking as well as from electron microscopy maps according to low map energies. Using a T-cell receptor variable domain and Acetylcholine Binding Protein (ACHBP) as example systems, we showed the application to model an energetic optimized complex structure according to a complex map. The map objects serves as a bridge between high resolution atomic structures and low resolution image data. Map restrained Self-guided Langevin dynamics simulation study of SARS-CoV-2 spike ectodomain The emergence of SARS-CoV-2 has resulted over 3 million infections and more than 200,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. It has been shown that SARS-CoV-2 S uses angiotensin-converting enzyme 2 (ACE2) to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. Coronavirus entry into host cells is mediated by the transmembrane spike (S) glycoprotein that forms homotrimers protruding from the viral surface . S comprises two functional subunits responsible for binding to the host cell receptor (S1 subunit) and fusion of the viral and cellular membranes (S2 subunit). Coronavirus entry into susceptible cells is a complex process that requires the concerted action of receptor-binding and proteolytic processing of the S protein to promote virus-cell fusion. As the coronavirus S glycoprotein is surface-exposed and mediates entry into host cells, it is the main target of neutralizing antibodies (Abs) upon infection and the focus of therapeutic and vaccine design. Conformational transition of SARS-CoV-2 spike is critical for its function to interact with ACE2 and enter host cells. The mechanism of the opening and possibility to mediate this process is the focus of research in development of vaccines. This research benefits from two main aspects, the information extraction from cryo-EM maps and the ability to reproduce the opening process. The map-restrained Self-guided Langevin dynamics method (MapSGLD) developed in this lab is a perfect tool for this type of research. This method accurately extract structure information from cryo-EM maps and achieve large scale conformational search through SGLD to achieve the goal of reproduce conformational evolvement from one state to another. Along the conformational path many opportunities for mediate the process can be discovered and studied. Current, the cryo-EM maps of the open and close state of the SARS-CoV-2 spike ectodomain are available, which provide us unprecedent opportunity to study the mechanism with MapSGLD. It is found that SARS-CoV polyclonal antibodies inhibit SARS-CoV-2 spike-mediated entry into cells. MapSGLD simulation of antibody-spike interaction will provide structure and energetic insight for vaccine development. Additional SARS-CoV2 simulations The SARS-Cov2 spike glycoprotein undergoes a structural transition in order to become activated and primed to infect humans. We have developed a workflow using our GPU hardware and OpenMM software that can quickly generate different mutations and protonation states of the spike protein, and simulate them with very high throughput. We are currently studying the role of protonation states in this conformational change to understand if, and how, varying pH can serve as a trigger for the cascade of events that lead to infection. Ionic Strength Induced Protein-Protein Interactions Protein kinases are dynamic and can adopt many conformational states, including active, inactive, and intermediate states which can represent an array of structural features that distinguish the ability of the protein to bind other molecules. Revealing the transitions between the conformational states of protein complexes is critical for effective rational design, as it would allow deeper insights into the structure function properties. Improper signaling of the nuclear factor-B (NF-B) pathway plays a critical role in many inflammatory disease states including cancer, stroke, and viral infections. While the signaling pathways are known, how these molecular mechanisms respond to changes in the intracellular microenvironment such as pH, ionic strength, and temperature, remains elusive. Molecular dynamics simulations were used to investigate how mutations and the ionic strength affect dimerization of the protein assembly to probe the affinity for tyrosine and serine phosphorylation activation mechanisms. Intermolecular interactions, thermodynamic properties, and conformational changes were compared among the inactive, active, and null states of the kinase. Results suggest that the multimeric assembly mediates a global stability for the enzyme that influences the activity of IKK and offers insight into which activation mechanism is preferred.", "keywords": [ "2019-nCoV", "Acetylcholine", "Adopted", "Affect", "Affinity", "Amber", "Antibodies", "Binding", "Binding Proteins", "Biological", "Cell fusion", "Cells", "Cellular Membrane", "Cessation of life", "Chemicals", "Classification", "Communities", "Complex", "Computational Technique", "Computer software", "Computing Methodologies", "Coronavirus", "Coronavirus spike protein", "Cryoelectron Microscopy", "Crystallization", "Data", "Development", "Dimerization", "Disease", "Docking", "Electron Microscopy", "Enzyme Stability", "Event", "Fluorescence Resonance Energy Transfer", "Glycoproteins", "Goals", "Human", "Image", "Infection", "Inflammatory", "Information Retrieval", "Ionic Strengths", "Lead", "Malignant Neoplasms", "Maps", "Mediating", "Methods", "Modeling", "Molecular", "Molecular Conformation", "Molecular Structure", "Mutation", "NMR Spectroscopy", "Nuclear", "Output", "Pathway interactions", "Peptidyl-Dipeptidase A", "Phosphorylation", "Phosphotransferases", "Play", "Process", "Property", "Protein Kinase", "Protein Region", "Proteins", "Proteolytic Processing", "Receptor Cell", "Research", "Research Support", "Resolution", "Roentgen Rays", "Role", "SARS coronavirus", "Serine", "Signal Pathway", "Signal Transduction", "Spectrum Analysis", "Stroke", "Structure", "Study models", "Surface", "System", "T-Cell Receptor", "Techniques", "Temperature", "Therapeutic", "Thermodynamics", "Tyrosine", "Vaccine Design", "Variant", "Viral", "Virus", "Virus Diseases", "Work", "X-Ray Crystallography", "conformational conversion", "design", "disease-causing mutation", "electron tomography", "experimental study", "inhibiting antibody", "insight", "intermolecular interaction", "macromolecular assembly", "macromolecule", "models and simulation", "molecular assembly/self assembly", "molecular dynamics", "molecular modeling", "molecular size", "neutralizing antibody", "peptide structure", "polyclonal antibody", "programs", "protein complex", "protein protein interaction", "protein structure", "protonation", "receptor binding", "simulation", "structural biology", "three dimensional structure", "tomography", "tool", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "7738", "attributes": { "award_id": "1ZIAHL001050-23", "title": "Molecular Dynamics Simulations Of Biological Macromolecules", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 1067238, "principal_investigator": { "id": 23533, "first_name": "Bernard R", "last_name": "Brooks", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1602, "ror": "", "name": "NATIONAL HEART, LUNG, AND BLOOD INSTITUTE", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1602, "ror": "", "name": "NATIONAL HEART, LUNG, AND BLOOD INSTITUTE", "address": "", "city": "", "state": "", "zip": "", "country": "United States", "approved": true }, "abstract": "pH dependance of a Na channel Sodium ion channels play an important role in electrical signaling in cells; as such they are the targets of many drugs, as well as naturally occurring toxins from plant and animal sources. Inhibition and/or improper functioning of sodium channels due to mutation can lead to disease. In bacterial voltage gated sodium channels, the passage of sodium ions through the pore is controlled by a selectivity filter (SF) comprised of four glutamate residues. The number of ions bound in the channel can vary, but is about 2 on average. We have shown with MD simulations at constant pH and with free energy perturbation that the pKa values of the four SF glutamate residues depend on the number of ions bound in the channel. With 2 or 3 ions bound, at physiological pH, the SF is most likely in fully deprotonated state, and possibly also the singly protonated state. With 1 or 0 ions bound, the doubly protonated state can also get populated. Based on the MD simulations of the fully open channel, we have further shown that the conductance of the channel decreases with each proton bound to the SF. Thus the conductance of the channel is pH dependent, and decreases with lowering of pH. We also show that the conductance depends on the lipid composition of the membrane. The mechanisms involved in modulation of the channel conductances involves changes in the radius of the gate and the SF, as well as the electric field in the pore. Mechanism of degradation of Histatin 5 peptide by Secreted Aspartic Protease (SAPS) of C. Albicans This project started with testing the double link atom (DLM) methodology to treat the boundary between QM and MM regions on Amino Acids. The charge of MM link atom for Amino Acids was optimized by minimizing the difference between the dipole of the molecule before and after removing the QM part. Next, mechanism of cleavage of Hst5 by Sap-2 the major produced Aspartic Protease of C. Albicans and the effect of mutation on the cleavage process was studied with QM/MM methodology. Docking the peptide to the active site of Saps is performed by restraining the distance between the active site aspartic (Asp) residues and the lysine (Lys) residue on Hst5. To find difference between binding of Hst5 and its mutants to SAP we performed replica exchange umbrella sampling (REUS) of the peptide by pulling the peptide from active site to bulk water phase. The results showed a -11 kcal/mol free energy of binding for Hst5 to SAP. Initial conformation for quantum region is obtained by putting a harmonic restraint between Lys of the peptide and Asp of the enzyme and it is observed that water molecules occupy the active site. Intermediate and product states of the reaction are produced by restrained QMMM optimization with DFT level of theory for quantum region. The mechanism involves a tetrahedral gem-diol intermediate state which then leads to amide bond hydrolysis. A replica path method in CHARMM was used to find transition state and minimum energy path (MEP) of the reaction with Hartree Fock (HF) level of theory of QM region with 6-31G basis set. It was found that the formation of the intermediate state is the limiting step of the reaction. However, a higher level of theory and a more complex basis set is now being used to confirm these results. In the next step, we will use the optimized reaction path to start an off-path sampling which allows us to find the free energy of the reaction. Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by MD simulations: The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virions surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). In this study we have provided a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Our results showed that nCOV-2019 RBD binds ACE2 with a significantly higher affinity () than SARS-COV which correlates with its higher infection rate. A per-residue free energy decomposition pinpointed the critical role of nCOV-2019 RBD residues Lys417, Tyr505, Gln498, Gln493 in binding ACE2. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally occurring mutations to the RBD either slightly strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This means the virus had sufficient binding affinity to its receptor at the beginning of the crisis. This also have implications for any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become even more infectious. Exploring dynamics and network analysis of spike glycoprotein in SARS-COV-2 The ongoing pandemic caused by coronavirus SARS-COV-2 continues to rage with devastating consequences on human health and global economy. A spike glycoprotein on the surface of coronavirus mediates its entry into host cells and is the target of all antibody design efforts to neutralize the virus. The glycan shield of the spike helps the virus to evade the human immune response by providing a thick sugar-coated barrier against any antibody. To study the dynamic motion of glycans in the spike protein we performed microsecond-long MD simulation on the spike protein in two different states that correspond to the receptor binding domain in open or closed conformations. Analysis of this microsecond-long simulation revealed a scissoring motion on the N-terminal domain of neighboring monomers in the trimer. Role of multiple glycans in shielding of spike protein in different regions were uncovered by a network analysis. Centrality measurements in graph theory helped us identify glycans that play local or global roles in the network. It was found that the stalk region glycans have high local centralities which give rise to an effective shielding of this domain. On the other hand, breaches can be found in the apex of the spike protein for antibodies to bind and neutralize the virus. Role of several glycan such as N234 and N165 were pinpointed in the network of glycan. Microdomains of glycans were identified featuring a high degree of intra-communication in these microdomains and therefore most antibodies would bind to regions between these microdomains. An antibody overlap analysis revealed the glycans microdomains as well as individual glycans that inhibit access to the antibody epitopes on the spike protein. Our analysis showed that the spike protein is more vulnerable to antibodies when the RBD is in the open state. Overall, the results of this study provide detailed understanding of the spike glycan shield which must be considered for any rational antibody design project.", "keywords": [ "2019-nCoV", "Active Sites", "Address", "Affinity", "Amides", "Amino Acids", "Angiotensins", "Animal Sources", "Antibodies", "Aspartic Endopeptidases", "Basic Science", "Binding", "Biological", "Biophysics", "Candida albicans", "Cell Surface Receptors", "Cells", "Cessation of life", "Charge", "Communication", "Complex", "Computational Biology", "Coronavirus", "Development", "Disease", "Disease Outbreaks", "Docking", "Electron Microscopy", "Enzymes", "Epitopes", "Escape Mutant", "Evaluation", "Evolution", "Free Energy", "Gene Expression Profiling", "Glutamates", "Glycols", "Glycoproteins", "Health", "Hot Spot", "Human", "Hydrolysis", "Image Analysis", "Immune response", "Individual", "Ions", "Laboratories", "Lead", "Link", "Lipids", "Lysine", "Measurement", "Mediating", "Membrane", "Methodology", "Methods", "Modeling", "Molecular Conformation", "Motion", "Multienzyme Complexes", "Mutation", "N-terminal", "National Heart Lung and Blood Institute", "Pathway Analysis", "Peptides", "Pharmaceutical Preparations", "Phase", "Physiological", "Plant Sources", "Play", "Polysaccharides", "Process", "Proteins", "Protons", "Quantum Mechanics", "Quantum Theory", "Radial", "Reaction", "Research", "Research Project Grants", "Role", "SARS coronavirus", "Sampling", "Scanning", "Science", "Scientist", "Signal Transduction", "Sodium Channel", "Structure", "Structure-Activity Relationship", "Surface", "System", "Techniques", "Testing", "Thick", "Toxin", "Vaccine Design", "Virion", "Virus", "Water", "base", "biophysical properties", "design", "drug development", "economic impact", "electric field", "graph theory", "histatin 5", "in silico", "infection rate", "interest", "macromolecule", "molecular dynamics", "molecular mechanics", "molecular modeling", "monomer", "mutant", "mutation screening", "novel coronavirus", "pandemic disease", "pharmacophore", "programs", "quantum", "receptor", "receptor binding", "restraint", "simulation", "small molecule", "sodium ion", "sugar", "theories", "tool", "voltage" ], "approved": true } }, { "type": "Grant", "id": "7739", "attributes": { "award_id": "1ZIAAG000581-01", "title": "Molecular Characterization of the SARS-CoV-2 Helicase and High-Throughput Screening to Identify Small Molecule SARS-CoV-2 Helicase Inhibitors as Anti-Viral Medicines", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 30287, "principal_investigator": { "id": 23534, "first_name": "Robert", "last_name": "Brosh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1613, "ror": "https://ror.org/049v75w11", "name": "National Institute on Aging", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1613, "ror": "https://ror.org/049v75w11", "name": "National Institute on Aging", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 Pandemic caused by the novel Severe Acute Respiratory Syndrome (SARS)- Coronavirus (CoV)-2 has necessitated prompt action by biomedical researchers to study key steps in the virus life cycle and identify viral replication targets for molecular interventions leading to therapeutic options. This project focuses on molecular characterization of SARS-CoV-2 (Nsp13) helicase essential for coronavirus replication. Analyses of SARS-CoV-2 helicase will advance our fundamental understanding of its mechanism-of-action and partnership with SARS-CoV-2 Nsp12 RNA-dependent RNA polymerase1. High-throughput screens to identify small molecules that interfere with catalytic functions and interactions of SARS-CoV-2 helicase will provide a strategy for crippling viral replication, a paradigm that builds upon ongoing studies of the Nsp12 polymerase targeting compound Remdesivir2. Discovery of candidate COVID-19 helicase inhibitors may lead to a novel therapeutic anti-viral approach applicable as mono-therapy or combination therapy with anti-viral drugs in use or development. COVID-19 poses a special challenge for the aging population who often have underlying medical conditions3. Age-related comorbid conditions, immuno-senescence, higher risk for infection and sickness in nursing homes, and complications of social distancing for older people likely contribute to elevated risk of mortality for aged individuals. Immune dysfunction and compromised virus (immune) pathogenesis are significant factors influencing the efficacy of future vaccines against COVID-19 for the elderly. Consequently, anti-viral therapies, ultimately combined with immunological strategies, will be advantageous. This COVID-19 research proposal is focused on a key SARS-CoV-2 replication target (helicase) and discovery of small molecule inhibitors as antiviral medicines.", "keywords": [ "2019-nCoV", "Antiviral Agents", "Antiviral Therapy", "Biochemical", "Biological Assay", "COVID-19", "COVID-19 pandemic", "Collection", "Combined Modality Therapy", "Coronavirus", "Crystallization", "Development", "Elderly", "Future", "Goals", "Immune", "Immune System Diseases", "Immunologics", "Individual", "Intervention", "Lead", "Life Cycle Stages", "Medical", "Medicine", "Molecular", "Molecular Bank", "Molecular Target", "Nucleic Acids", "Nucleotides", "Nursing Homes", "Pathogenesis", "Polymerase", "Proteins", "RNA", "RNA Polymerase III", "RNA-Directed RNA Polymerase", "Research Personnel", "Research Proposals", "Resolution", "Social Distance", "Structure", "Structure-Activity Relationship", "Therapeutic", "Vaccines", "Virus", "Virus Replication", "age related", "aged", "aging population", "biophysical properties", "comorbidity", "helicase", "high risk", "high throughput screening", "immunosenescence", "infection risk", "inhibitor/antagonist", "mortality risk", "novel", "novel therapeutics", "repository", "small molecule", "small molecule inhibitor", "small molecule libraries" ], "approved": true } }, { "type": "Grant", "id": "7740", "attributes": { "award_id": "1ZIAMH002969-02", "title": "Unit on Neuroscience and Novel Therapeutics", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 1425268, "principal_investigator": { "id": 23535, "first_name": "Melissa", "last_name": "Brotman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1604, "ror": "https://ror.org/04xeg9z08", "name": "National Institute of Mental Health", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1604, "ror": "https://ror.org/04xeg9z08", "name": "National Institute of Mental Health", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "In 2020, our program completed a randomized controlled trial (N=44, active vs. placebo) of a computer-based treatment engaging behavioral and neural targets of aberrant threat processing. In addition, we developed an analogous fMRI paradigm to probe neural correlates in a large (N>100) sample of youth with varying degrees of irritability. We found unique neural correlates associated with latent factor-derived phenotype of high irritability and anxiety. Second, we developed a novel frustration-exposure intervention for youth with severe irritability based on extinction principles. N=30 youth have been randomized; preliminary analyses demonstrated that irritability scores decreased significantly from the start of therapy to end of therapy. NNT acquires pre-treatment behavioral and task-based fMRI data to test the hypothesis that pre-treatment behavioral deficits in inhibition predict poorer treatment response. Third, we leverage technology to assess symptoms by utilizing digitally based event sampling (ecological momentary assessment). We have also developed a cognitive inhibition mobile application to probe children's inhibitory control. These interventions provide the foundation for scalable, target-based interventions which are more easily disseminated, facilitating public health impact. Fourth, as threats engage evolutionarily conserved processes, our translational perspective has been supported by two Bench-to-Bedside Awards. Specifically, we reverse translated the Human Intruder Paradigm, (Kalin & Shelton 1989) into two clinical paradigms. Our fMRI (N=60) and eye-tracking (N=60) tasks parallel work in non-human primates. Ultimately, these mechanistic studies will allow for more targeted interventions for pathological irritability. Finally, the acute onset of the COVID-19 pandemic provides a rare opportunity to utilize existing pre-stress clinical and neural data to predict stress-related increases in psychopathology and associated neural dysfunction. In this study, we are examining associations among stress, genetic liability, brain function, and the development of psychopathology.", "keywords": [ "Acute", "Address", "Affect", "Anxiety", "Award", "Base of the Brain", "Behavior Therapy", "Behavioral", "Behavioral Mechanisms", "Brain", "COVID-19 pandemic", "Child", "Childhood", "Clinical", "Clinical Trials", "Cognitive", "Complex", "Computer Models", "Computers", "Coupled", "Data", "Development", "Ecological momentary assessment", "Event", "Extinction (Psychology)", "Foundations", "Frustration", "Functional Magnetic Resonance Imaging", "Genetic", "Goals", "Human", "Impairment", "Intervention", "Lead", "Learning", "Mental disorders", "Metabolic", "Neuronal Dysfunction", "Neurosciences", "Outcome", "Pathologic", "Pharmaceutical Preparations", "Phenotype", "Placebos", "Process", "Protocols documentation", "Psychopathology", "Public Health", "Randomized", "Randomized Controlled Trials", "Sampling", "Social Environment", "Stress", "Symptoms", "Taxonomy", "Technology", "Testing", "Translating", "Work", "Youth", "base", "bench to bedside", "clinical phenotype", "digital", "mobile application", "mobile computing", "negative affect", "neural correlate", "neuromechanism", "nonhuman primate", "novel", "novel therapeutics", "programs", "psychologic", "relating to nervous system", "response", "side effect", "translational neuroscience", "treatment response", "visual tracking" ], "approved": true } }, { "type": "Grant", "id": "7743", "attributes": { "award_id": "1ZIAAI000938-17", "title": "Paramyxoviruses as Vaccine Vectors Against Highly Pathogenic Viruses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 279642, "principal_investigator": { "id": 23540, "first_name": "Ursula", "last_name": "Buchholz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "We previously constructed a first-generation construct called HPIV3-EbovZ GP, in which the complete genome of the JS strain of HPIV3 was modified by the addition of the EBOV GP gene in the third gene position, between the HPIV3 P and M genes. The JS strain is thought to be an attenuated HPIV3, based on previous clinical studies, although the basis of this attenuation is unknown. EBOV GP is the sole EBOV virion surface protein, the sole EBOV neutralization antigen, and the major protective antigen. The EBOV GP gene was engineered to have the appropriate HPIV3 transcription signals for it to be expressed as a separate mRNA by the HPIV3 polymerase. HPIV3-EbovZ GP was substantially immunogenic and protective when given to non-human primates by combined intranasal (IN) and intratracheal (IT) administration, even in animals previously infected with HPIV3. However, immunogenicity depended on IT delivery of vaccine: IN delivery alone was insufficient. This suggested that vector expression beyond the upper respiratory tract was necessary for immunogenicity. We therefore explored delivery of the HPIV3-EbovZ GP construct by the aerosol route in rhesus macaques. The aerosol route was generally more immunogenic and protective than the combined IN/IT route. This induced generally higher serum and mucosal EBOV-specific IgG, IgA, and neutralizing antibody titers, as well as EBOV-specific cellular responses in the lungs, including polyfunctional CD8+ T cells and CD4+ T helper cells that were predominately Th1. In addition, the HPIV3-EbovZ GP vaccine induced more robust cell-mediated and humoral immune responses than an alphavirus vaccine delivered parenterally in parallel. One aerosol dose of HPIV3-EbovZ GP conferred 100% protection to macaques against EBOV challenge. We developed a second-generation version of this vector, called HPIV3/delHNF/EbovZ-GP, in which the HPIV3 F and HN genes were deleted, leaving EBOV GP as the sole viral surface glycoprotein. A large comparative study in cynomolgus monkeys by our collaborator Alexander Bukreyev at the University of Texas Medical Branch, Galveston, (who made the construct while a Staff Scientist in LID/NIAID) showed that this second-generation version was even more protective than the first-generation even though it was very highly restricted for replication (much more restricted than the first-generation construct). We performed (with clinical collaborators at the Johns Hopkins Bloomberg School of Public Health) an open label phase 1 clinical trial to determine the safety, tolerability, and immunogenicity of HPIV3-EbovZ GP delivered IN in healthy adults in an inpatient setting (NCT025645750), which was intended to be a safety study prior to evaluating aerosol delivery. Ten subjects received two doses (4- to 8-week interval) of 6.0 log10 PFU of vaccine. The first dose was moderately infectious (7/10 subjects shed virus detected by qRT-PCR, mean peak titer 3.8 log10 genomic equivalents/ml, mean duration of shedding 7.9 days). Little shedding was detected after the second dose. A second cohort (n=20) received one of two planned doses of 7.0 log10 PFU of vaccine. Shedding was similar but of shorter duration (mean of 3.7 days). The vaccine was well tolerated, with the exception that asymptomatic ALT elevations were noted in 5 volunteers (3 mild, 2 moderate) in cohort 2 after vaccination and associated with shedding. All resolved by day 28. The study was halted due to these elevations of ALTs, but their significance is unclear. Because of this, this vaccine will not be administered further at this time. Induction of serum antibodies was poor (mucosal antibodies not yet analyzed), but this was expected since, as noted above, we had previously observed that administration by the IN route alone was poorly immunogenic in rhesus monkeys. We have initiated a Phase 1 study to evaluate the safety, infectivity, and immunogenicity of two doses of the HPIV3/HNF/EbovZ GP vaccine candidate when administered intranasally in healthy adults in an inpatient setting (NCT03462004). Participants are being enrolled sequentially in two cohorts. Participants in Cohort 1 have been randomly assigned to receive two doses of either 6.0 log10 PFU/mL of HPIV3/delHNF/EbovZ-GP vaccine or placebo. The first dose was given on Day 0 and the second dose was given 35 days later. Vaccine replication was evaluated by nasal wash and RT-qPCR and infectivity assays, and serum antibody responses will be measured. As expected, at the 6.0 log10 PFU dose, the HPIV3/HNF/EbovZ-GP vaccine was marginally infectious, and adverse events were generally mild to moderate. The study was deemed safe to proceed to the evaluation of the higher 7.0 log10 PFU dose after the closures due to the current SARS-CoV-2 pandemic will be lifted. Participants in Cohort 2 will be randomly assigned to receive two doses of either 7.0 log10PFU/mL of HPIV3/HNF/EbovZ-GP vaccine or placebo on Days 0 and 28.", "keywords": [ "2019-nCoV", "Adult", "Adverse event", "Aerosols", "Alphavirus", "Animals", "Antibodies", "Antibody Response", "Antibody titer measurement", "Antigens", "Attenuated", "Avian Influenza A Virus", "Avulavirus", "Biological Assay", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "Cattle", "Cavia", "Cell Culture Techniques", "Cells", "Child", "Chimera organism", "Clinical", "Clinical Research", "Comparative Study", "Coronavirus spike protein", "Development", "Dose", "Ebola virus", "Ebola virus envelope glycoprotein", "Effectiveness", "Engineering", "Enrollment", "Evaluation", "Family member", "Gene Order", "Generations", "Genes", "Genetic Transcription", "Genome", "Genomics", "Glycoproteins", "Human", "Immune response", "Immunity", "Immunoglobulin A", "Immunoglobulin G", "Infant", "Infection", "Influenza Hemagglutinin", "Inpatients", "Intranasal Administration", "Lifting", "Lung", "Macaca", "Macaca fascicularis", "Macaca mulatta", "Measures", "Mediating", "Medical", "Membrane Glycoproteins", "Membrane Proteins", "Messenger RNA", "Modification", "Mucosal Immunity", "Mucous Membrane", "National Institute of Allergy and Infectious Disease", "Newcastle disease virus", "Nose", "Para-Influenza Virus Type 1", "Para-Influenza Virus Type 3", "Paramyxovirus", "Participant", "Pathogenicity", "Phase I Clinical Trials", "Placebos", "Polymerase", "Population", "Primates", "Proteins", "Public Health Schools", "Quantitative Reverse Transcriptase PCR", "RNA", "Randomized", "Respiratory System", "Rodent", "Route", "SARS coronavirus", "Safety", "Scientist", "Serotyping", "Serum", "Severe Acute Respiratory Syndrome", "Signal Transduction", "Structure of respiratory epithelium", "Surface Antigens", "System", "TRIP10 gene", "Testing", "Texas", "Time", "United States National Institutes of Health", "Universities", "Upper respiratory tract", "Vaccination", "Vaccines", "Viral", "Viral Vaccines", "Virion", "Virus", "Virus Replication", "Virus Shedding", "Work", "attenuation", "base", "cohort", "conjunctiva", "design", "expression vector", "immunogenic", "immunogenicity", "neutralizing antibody", "nonhuman primate", "open label", "pandemic disease", "parainfluenza virus", "pathogen", "pathogenic virus", "phase 1 study", "respiratory", "response", "reverse genetics", "safety study", "seropositive", "tissue tropism", "vaccine candidate", "vaccine delivery", "vaccine development", "vector", "vecto" ], "approved": true } }, { "type": "Grant", "id": "7744", "attributes": { "award_id": "1ZIAAI001298-01", "title": "Paramyxoviruses as Vaccine Vectors Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [], "start_date": null, "end_date": null, "award_amount": 787601, "principal_investigator": { "id": 23540, "first_name": "Ursula", "last_name": "Buchholz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1540, "ror": "https://ror.org/043z4tv69", "name": "National Institute of Allergy and Infectious Diseases", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "There are no vaccines to protect against SARS-CoV-2 infection and COVID-19 disease caused by SARS-CoV-2. Effective vaccines are urgently needed. Paramyxovirus vectors expressing an immunogenic version of the SARS-CoV-2 S protein would provide novel live vaccines for intranasal administration, designed to be highly attenuated in humans while maintaining a high level of immunogenicity at the primary sites of infection of SARS-CoV-2. A major emphasis is being put on developing paramyxovirus vector vaccines that should not be restricted by pre-existing immunity in the human population. These viral vectors are designed to replicate in the superficial layers of the respiratory epithelium, inducing local mucosal and systemic innate immunity, virus-neutralizing serum antibodies, and CD8+ and CD4+ T cells. Intranasal paramyxovirus vector vaccines would provide systemic and local protection in the respiratory tract, the primary site of SARS-CoV-2 infection, and, similar to other live viral vaccines, are expected to rapidly induce immunity following a single dose of vaccine. Large quantities of vaccine doses could be generated rapidly.", "keywords": [ "2019-nCoV", "African Green Monkey", "Antibodies", "Attenuated", "Attenuated Vaccines", "CD4 Positive T Lymphocytes", "CD8B1 gene", "COVID-19", "Cattle", "Development", "Disease", "Disease Outbreaks", "Dose", "Human", "Immunity", "Immunization", "Infection", "Intranasal Administration", "Modeling", "Mucous Membrane", "Natural Immunity", "Para-Influenza Virus Type 3", "Paramyxovirus", "Population", "Proteins", "Respiratory System", "SARS coronavirus", "Serum", "Severe Acute Respiratory Syndrome", "Site", "Structure of respiratory epithelium", "Vaccines", "Viral Vaccines", "Viral Vector", "Virus", "base", "conjunctiva", "design", "immunogenic", "immunogenicity", "neutralizing antibody", "nonhuman primate", "novel", "pandemic disease", "pathogen", "response", "vaccine candidate", "vector", "vector vaccine" ], "approved": true } }, { "type": "Grant", "id": "7749", "attributes": { "award_id": "75N92019D00033-P00002-759201900074-1", "title": "REDS-IV-P - CENTER FOR TRANSFUSION LABORATORY STUDIES (CTLS) - SARS-CoV-2/COVID-19 STUDIES", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2019-04-01", "end_date": "2021-03-31", "award_amount": 4748941, "principal_investigator": { "id": 23549, "first_name": "MICHAEL Paul", "last_name": "BUSCH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1617, "ror": "", "name": "VITALANT", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1617, "ror": "", "name": "VITALANT", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "This project will focus on key blood safety issues with COVID-19 and further our understanding of SARS-CoV-2 natural history and pathogenesis.", "keywords": [ "2019-nCoV", "Blood", "Blood Transfusion", "COVID-19", "Laboratory Study", "Natural History", "Pathogenesis", "Prevention", "Safety", "Transfusion", "transmission process" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1442, "count": 14420 } } }