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Award details
Development of a virus-free sensor system to repurpose approved drugs for blocking Coronavirus replication
Reference
BB/V017780/1
Principal Investigator / Supervisor
Dr Betty Chung
Co-Investigators /
Co-Supervisors
Institution
University of Cambridge
Department
Pathology
Funding type
Research
Value (£)
235,445
Status
Completed
Type
Research Grant
Start date
01/02/2021
End date
28/02/2023
Duration
25 months
Abstract
unavailable
Summary
The COVID19 pandemic has highlighted the importance of timely discovery of antiviral therapeutics, especially when there is little information as to whether vaccines developed (and pending approval) enable a significant period of immunity. Therefore the development of cost effective, high-throughput sensor systems to rapidly repurpose approved drugs as antiviral agents is extremely desirable. We have developed a virus-free sensor system - pShiftSensor that can specifically screen for drugs to block SARS-CoV2 replication by inhibiting the ribosomal frameshift that is essential for production of the viral replicase. The sensor system is fluorescent-based, therefore permitting cost-effective high-throughput quantitate readout. The system is based on the cis-element required for -1 programmed ribosomal frameshifting (-1 PRF), a non-canonical translation mechanism that is ubiquitous throughout all coronaviruses and used to synthesis viral proteins including the RNA-dependent RNA polymerase (RdRP), essential for viral replication. We have developed pShiftSensor-v1, which is a dual-reporter system that contains the SARS-CoV-2 -1PRF cassette (i.e. the slippery sequence UUUAAAC and the 3' pseudoknot). The system is bi-cistronic thereby avoiding expression artifacts due to differential delivery between the control and test reporter expression cassette. Through this proposal, we will upgrade our system to pShiftSensor-V2, which targets primary cell types such as small airway lung cells, the key entry cell type for SARS-CoV2 infection, and primary leukocytes, especially monocytes/macrophages and T-cells, essential for systemic infection. pShiftSensor-V2 will permit cost-effective, high-throughput cell-type specific screening of viral replication inhibitory compounds in a physiological environment.
Committee
Not funded via Committee
Research Topics
Microbiology, Technology and Methods Development
Research Priority
X – Research Priority information not available
Research Initiative
Covid19 Rapid Response [2020]
Funding Scheme
X – not Funded via a specific Funding Scheme
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