10000 documents

Structural and functional studies of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Nadine Samara · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · 2021 · $467,822 — GalNAc-Ts are Golgi-membrane anchored enzymes containing 2 luminal domains that dictate substrate specificity: a catalytic domain and a C-terminal lectin domain consisting of 3 repeats (alpha, beta, gamma) that can potentially recognize and bind extant GalNAcs on glycoprotein or glycopeptide substra…

Pathogenesis, Treatment and Prevention of Emerging Infectious Diseases

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

H. Clifford Lane · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $155,251 — Research in this project is currently focused on six areas. These are: characterization of the survivors of the anthrax attacks of 2001; characterization of emerging respiratory infections including SARS, COVID-19, and influenza; evaluation of experimental vaccines and treatments for Ebola virus; c…

COVID-19: Identification and Development of Clinical Candidates to Treat SARS-CoV-2

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Donald Lo · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · 2021 · $3,643,319 — We have worked in collaboration with experts in and outside of NIH on the development of 8 assays for use in repurposing screens of approved drug collections to identify compounds active against SARS-CoV-2. The compounds identified from such screens have potential for clinical trials as single agent…

Molecular imaging of viral infections

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Dima A Hammoud · CLINICAL CENTER · 2021 — Sars-Cov-2 project: We have started our experiments by developing the LPS lung injury model by administering LPS intratracheally. We are using male and female mice, including WT and ACE2 Transgenic mice. At this stage we are imaging the lung infiltrates and assessing ACE2 levels in the various group…

COVID-19: Assay Development, HTS and Drug Repurposing to identify potential therapeutics against SARS-CoV-2

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Matthew Hall · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · 2021 · $462,178 — During this past reporting period, NCATS began development of over a dozen novel assays to screen for potential therapeutic agents against SARS-CoV-2. Optimized assays were then screened against a panel of drug repurposing, clinical candidate and antiviral libraries that have been assembled at NCAT…

Development of COVID-19 cell entry inhibitors

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Nadya Tarasova · DIVISION OF BASIC SCIENCES - NCI · 2021 · $61,708 — The reliability, and consequently success of virtual screening depends heavily on the accuracy of the x-ray structure depiction of the target protein structure in solution. Crystal packing can distort conformation of flexible parts of the protein thus leading to misrepresentation of the protein stru…

Antagonism of Coronavirus Spike Proteins by Cellular Host Factors

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

eric freed · DIVISION OF BASIC SCIENCES - NCI · 2021 · $18,681 — In a structural and functional analysis of the SARS-CoV-2 S protein that we recently started, we have determined that MARCH8, but not a catalytically inactive MARCH8 mutant, targets the S proteins of SARS-CoV, MERS-CoV, and SARS-CoV-2 for degradation. We also showed that human airway epithelial cell…

Transgenic Resources for Neuroscience Research

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

James Pickel · NATIONAL INSTITUTE OF MENTAL HEALTH · 2021 · $2,338,230 — Summary 1) Production of rodent transgenics Metrics of production over the past year include the following projects: a) 19 transgenic rodent projects produced by CRISPR constructs, with multiple lines produced for each project in rats (4) or mice (15). b) only 4 projects used legacy methods to make…

Serologic studies of persons with COVID-19 infection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Jeffrey Cohen · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $11,170 — Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related disease and death. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune re…

COVID-19 Serosurveys and Vaccine Study Site Preparations

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Patrick Duffy · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $780,824 — LMIV produced and obtained antigens for multiple COVID-19 serology assays. First, plasmids were obtained for production of full-length spike and RBD used in the assay developed by Florian Krammer at Mount Sinai Hospital in New York. After 3 successful production runs of COVID-19 spike proteins used…

The Glycan Shield of the SARS-Cov-2 Spike; Antigenicity and Function

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

JAMES L ARTHOS · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $92,584 — We have produced various versions of a recombinant SARS-CoV-2 Spike glycoproteins that differ in their glycan content. We then characterized the way in which these differentially glycosylated forms of the spike interact with ACE2, and various lectin receptors (e.g L-SIGN, DC-SIGN). In addition, we a…

COVID vaccine-associated allergic reactions

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Pamela Guerrerio · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $35,184 — The SARS-CoV-2 virus has incited a global pandemic leading to profound loss of human life and tremendous economic and social upheaval. In late 2020, the FDA issued emergency use authorizations (EUAs) for mRNA vaccines produced by Pfizer-BioNTech and Moderna that were found to be highly effective in …

Coronavirus vaccine development

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Barney Graham · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $522,460 — When the MERS CoV outbreak raised global health concerns, we initiated a program to develop a candidate vaccine. Based on prior studies to solve the spike structure of HKU1 (an endemic betacoronavirus) and finding stabilizing mutations that also stabilized MERS-CoV and SARS-CoV spike proteins, and p…

Design of Antigenically-Specific Probes for Sera Analysis and MAb Isolation

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Tongqing Zhou · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $157,844 — An understanding of the serum responses of virus-infected individuals and vaccinees is critical for the development of effective vaccines against HIV-1, SARS-CoV-2 and other viral pathogens. Perhaps the most important biological aspect of a serum response is its neutralizing activity, with a close s…

Adaptive MERS coronavirus-cell entry pathways and their relevance to virulence and antiviral strategies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Thomas Miller Gallagher · UNIVERSITY OF IOWA · 2021 · $266,291 — PROJECT SUMMARY The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic virus that can cause fatal disease in patients with underlying comorbidities. Further recognition of this respiratory syndrome and prevention strategies will require a small animal infection model as well as an…

Open Drug Discovery Center for Alzheimer's Disease

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

ALLAN I LEVEY · EMORY UNIVERSITY · 2021 · $848,836 — The Open Drug Discovery Center for AD (Open-AD) Structural Biology core aims to provide Target Enabling Packages (TEPs): a combination of experimental tools and knowledge that will allow researchers to investigate the biology of potential drug targets and to test therapeutic hypotheses. The TEPs wil…

Project 2: PanbetaCoV protein vaccine design

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Kevin Wiehe · DUKE UNIVERSITY · 2021 · $4,217,384 — Abstract – Project 2 Animal betacoronaviruses (betaCoVs), such as those that gave rise to SARS-CoV-1, MERS, and now SARS- CoV-2, represent a significant, continuous threat to human health. Vaccines can provide pre-existing immunity to future zoonotic coronaviruses. A major limitation of the current …

Integrative Immunogen Design and Testing

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Erica Ollmann Saphire · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $2,628,877 — Project 3 Summary Coronaviruses will likely remain a persistent threat to human health. However, whether the next significant disease outbreak will be caused by a known coronavirus, another novel coronavirus, or continued surges from variant(s) of SARS-CoV-2 is unknown. The goal of this project is t…

Cross-Protective Humoral Immunity to Coronavirus

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Duane R. Wesemann · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $3,169,124 — PROJECT 1 SUMMARY Global establishment of Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is a continued human threat. While successful vaccine programs are well underway, genetic drift and immune escape have already begun to subvert immunity. In addition, related zoonotic coronaviruses…

Immunogenicity and Efficacy of SARS-CoV-2 stabilized prefusion Spike protein vaccines in infant rhesus macaques

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Kristina De Paris · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $46,196 — ABSTRACT – Overall Nearly 600,000 new HIV infections occur yearly in adolescents/young adults (ages 15-24 years), the only population in which HIV infections continue to rise. The end of the HIV/AIDS epidemic will be achievable only when an effective vaccine regimen can elicit long-term protective i…