权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Imaging SARS-CoV-2 proteases for spatio-temporal insight into Covid-19

对 SARS-CoV-2 蛋白酶进行成像以时空洞察 Covid-19

基本信息

批准号：
10167571
负责人：
Jesse Vincent Jokerst
金额：
$ 43.39万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10167571
关键词：
2019-nCoV Adult Aftercare Animal Model Antibodies Biodistribution Biological Assay Biological Phenomena COVID-19 Cells Chemistry Chromatography Communicable Diseases Communities Complex Contrast Media Coronavirus Infections Coupled DegP protease Detection Development Disease Disease Reservoirs Drug Targeting Energy Transfer Excision Exposure to Fluorescence Genes Goals Image Imaging Device In Vitro Infection Light Literature Location Maps Mass Chromatography Mass Spectrum Analysis Measures Mediating Methods Modeling Monitor Mus Nanotechnology Nature Neonatal Noise Normal tissue morphology Organ Organism Paper Patients Peptide Hydrolases Photons Population Production Proteins Publishing Reaction Reagent Recombinants Reporting Research Rodent Model Route Saliva Sampling Screening procedure Serologic tests Serum Severe Acute Respiratory Syndrome Signal Transduction Sindbis Virus Societies Swab Testing Time Tissues Viral Viral Load result Viral Vector Viral reservoir Virus Virus Replication Work Zika Virus acoustic imaging animal imaging base chemical synthesis contrast imaging cost design experience human disease human model imaging agent imaging approach imaging modality in vitro testing in vivo in vivo Model in vivo imaging innovation insight latent infection nano neonate optical imaging pathogen research study response spatiotemporal targeted imaging temporal measurement tissue culture tool

项目摘要

Project summary/abstract: This work will build a contrast agent for the SARS-CoV-2 main protease (Mpro; also known as 3CLpro) and validate it in an animal model. This contrast agent will have significant value as a research tool because it will map and measure Mpro with spatial and temporal resolution. Conventional methods to studying SARS-CoV-2 are based on PCR and serology. These are powerful and affordable tools for population-wide studies but have limited value in research studies because they are in vitro tools that use single time-point sampling. They cannot monitor the biodistribution and time course of the viral load in vivo or detect the location of viral reservoirs. In contrast, in vivo imaging offers the ability to track biological phenomena longitudinally, quantitatively, and relatively non-invasively. Thus, Aim 1 of this proposal will build a contrast agent for Mpro based chemiluminescent resonant energy transfer (CRET). Chemiluminescence is a very useful in vivo imaging tool because it measures spontaneous emission of photons from contrast agents. Thus, the background emission of normal tissue is zero leading to high sensitivity imaging in contrast to in vivo fluorescence that suffers from high background. When in the CRET configuration, the probe is silent; activation via a Mpro-cleavable sequence leads to high signal. We will validate these CRET-based molecules with chemistry and recombinant Mpro. Aim 2 will validate this probe with a Sindbis virus models of SARS-CoV-2. We are using this Sindbis model because it is suitable for BSL-2 labs allowing work to proceed immediately unlike wild type SARS- CoV-2 requiring BSL-3. We will express Mpro via Sindbis virus in tissue culture and animal models and image viral progression in adult and neonate mice. After validating this contrast agent and imaging approach, the community will have a powerful tool to answer many important questions related to SARS-Cov-2 infection: What is the time course of infection and biodistribution?; How does biodistribution change by route of infection? Are there latent disease reservoirs?; How do protease levels change in response to therapy? This work is innovative because it will be the first example of in vivo Mpro imaging. The significance is motivated by the profound impact Covid-19 has had on our society. Importantly, the work is feasible based it will harness Dr. Jokerst’s extensive experience in chemistry and contrast agent development as well as Dr. Siqueira-Neto’s expertise in infectious disease including Zika virus.

项目总结/文摘:

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Goldilocks Energy Minimum: Peptide-Based Reversible Aggregation and Biosensing.

金发姑娘能量最低：基于肽的可逆聚集和生物传感。

DOI：
10.1021/acsami.3c09627
发表时间：
2023
期刊：
ACS applied materials & interfaces
影响因子：
9.5
作者：
Yim,Wonjun;Retout,Maurice;Chen,AmandaA;Ling,Chuxuan;Amer,Lubna;Jin,Zhicheng;Chang,Yu-Ci;Chavez,Saul;Barrios,Karen;Lam,Benjamin;Li,Zhi;Zhou,Jiajing;Shi,Lingyan;Pascal,TodA;Jokerst,JesseV
通讯作者：
Jokerst,JesseV