A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
PROJECT SUMMARY/ABSTRACT The primary objective of this proposal is to explore the ability of coordination complexes to serve as coordinate covalent inhibitors of cysteine proteases. We propose a hit-to-lead, systematic, proof-of-concept to syntheisize, characterize, and demonstrate the ability of Re(I) transition metal complexes to inhibit the SARS-CoV-2 main protease (3CLpro). To identify inhibitors of 3CLpro, this proposal will complete two specific aims. In Specific Aim 1, we will employ a library of bidentate ligands to generate ~150 distinct [Re(CO)3(L)(X)] complexes where ‘L’ represents different bidentate ligands and ‘X’ represents a leaving group (e.g., H2O). These complexes will be evaluated for their stability in buffer, reactivity with amino acids, and activity against 3CLpro. Specific Aim 1 will provide the initial hits to feed into Specific Aim 2. In Specific Aim 2, the most active hits identified in Specific Aim 1 will be further elaborated to establish a structure-activity relationship (SAR) and drive hit-to-lead development against 3CLpro. A typical design- synthesize-test iterative cycle will be used to develop the SAR and obtain increasingly better inhibitors. Upon completion of Specific Aim 2, we will complete the hit-to-lead effort, with the goal of obtaining at least one lead compound with an IC50 value of <50 nM against the SARS-CoV-2 3CLpro and good selectivity (IC50 >100 µM against non-target enzymes). This project will test the central hypothesis of whether metal-based compounds can provide a new class of covalent inhibitors against a relevant model target enzyme. Although not a drug discovery effort per se, our preliminary findings strongly suggest Re(I) complexes have the potential to generate potent and selective covalent inhibitors. In the long term, inhibitors derived from Re(I) complexes will demonstrate attractive features that are not readily achieved with conventional, organic inhibitors. For example, Re(I) compounds can be transformed into ‘theranostics’ simply by changing the choice of metal in (e.g., 99Tc). This proposal will provide a conceptual framework for exploring and exploiting the unique advantages afforded by metal-based therapeutics.
Grant Summary
A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $196K for university, nonprofit, healthcare org. Applications are due 2028-06-30 (open). Check eligibility and apply with FindGrants.
Not quite the right fit?
Search 9,000+ open grants, or get matches ranked for your organization — free.
Focus Areas
Eligibility
How to Apply
Up to $196K
2028-06-30
- 1Confirm your organization is eligible for A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NIAID - National Institute of Allergy and Infectious Diseases's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors: Frequently Asked Questions
Who is eligible for the A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors?
A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors provide?
A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors provides up to $196K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors deadline?
Applications for A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors are due 2028-06-30 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors?
To apply for A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.