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Nanobody toolkit for human coronavirus classification

用于人类冠状病毒分类的纳米抗体工具包

基本信息

批准号：
10375561
负责人：
ANDREW HAYHURST
金额：
$ 24.75万
依托单位：
TEXAS BIOMEDICAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-19 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10375561
关键词：
2019-nCoV Affinity Amino Acid Sequence Amino Acids Animals Antibodies Antibody Response Antigen Targeting Appearance Architecture Attention Binding Biological Assay Biological Markers Cells Classification Common Cold Communities Coronavirus Coronavirus Infections Coronavirus nucleocapsid protein Deposition Diagnostic Discrimination Disease Ecosystem Elements Ensure Enzyme-Linked Immunosorbent Assay Enzymes Epidemic Epitopes Escherichia coli Family Funding Future Genbank Genes Genome Goals Haptens Health Human Hybridomas Immune Sera Immunization Immunoglobulin G Individual Libraries Llama Logic Mediating Microscopy Middle East Respiratory Syndrome Middle East Respiratory Syndrome Coronavirus Minor Molecular Conformation Nucleocapsid Nucleocapsid Proteins Nucleoproteins Population Proteins RNA Reagent Recombinants Reporter Research Research Personnel Research Proposals Respiratory Disease Respiratory distress SARS coronavirus Sequence Homology Serum Severe Acute Respiratory Syndrome Specificity Structure System Technology Therapeutic Intervention United States National Institutes of Health Variant Virus Western Blotting Work Zoonoses antigen test base cross reactivity dimer follow-up global health human coronavirus human disease human pathogen in silico innovation milligram nanobodies novel novel coronavirus pandemic disease particle pathogen respiratory response screening seroconversion spillover event success zoonotic coronavirus zoonotic spillover

项目摘要

ABSTRACT The endemic human coronaviruses (HCoV) NL63, OC43, 229E and HKU1 have typically been associated with relatively mild and self-limiting respiratory disease resembling the common cold in healthy individuals. However, the newly emerging zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) can cause more severe respiratory distress, especially in those with underlying health conditions and can be fatal. Coronaviruses are diverse and spillover from zoonotic reservoirs either directly to humans or via an intermediate host. Spillover is likely to be more frequent due to the ever-expanding human population and ecosystem erosion, thereby ensuring more collisions between natural and unnatural host. Our exploratory research proposal seeks to develop a small toolkit of immunoreagents that will form the basis of a logic gate to identify and classify coronaviruses. A single immunoreagent, with broad recognition of overall shared protein architecture, will allow the identification of the coronavirus genera. Separate immunoreagents with absolute specificity for unique amino-acid variation between the human and zoonotic coronaviruses will allow the further classification to a known pathogen. Such a toolkit will quickly establish if a newly emerging virus is a coronavirus we are familiar with or is a novel genus or lineage that has never before spilled over into the human population and may demand urgent follow up for epidemic or pandemic potential. Our immunoreagents are based on llama single domain antibodies or nanobodies that are inexpensive to produce at high yields in E. coli and highly modular, allowing fusion to enzymatic reporter enzymes for one-step probing of virus infected cells and facile establishment of sandwich assays. Immortalization of nanobody sequences in silico means these are immediately available to the wider research community following deposition in Genbank unlike polyclonal sera or hybridomas secreting IgG. Single-pot library technology enables a rapid response to be mounted against any newly emerged coronavirus in the future, ensuring we are more pro-active than re-active to help safeguard human health.

摘要