Thursday, April 25, 2024
4/25/2024
Project Summary The pandemic COVID-19 has, as of April 13, 2020, infected nearly 2M individuals worldwide, with over 560,000 U.S. cases and over 22,000 U.S. deaths. There are no FDA approved vaccines or treatments for COVID-19. This supplemental proposal describes the accelerated development of such a drug, with potential near-term uses of these early therapeutic candidates for probing the structural-function relationships between the SARS-CoV-2 spike protein and the human ACE2 receptor protein. This work builds directly from Project 2 of the NCI-supported U54 NSBCC program. The specific aims of that project center around the technology of Protein Catalyzed Capture agents (PCCs),1 with a specific focus on developing technologies for the high-through production of PCCs, as well as an emphasis on drug-targeting the KRASG12D oncoprotein. A unique aspect of PCCs is that they are, by design, developed to bind to a specific epitope on a specific protein,2 thus providing an avenue for targeting an epitope containing a genetic mutation (relevant to oncoproteins),3 or providing an avenue for targeting epitopes that are broadly conserved, which bears relevance to targeting strategies aimed at the SARS- CoV-2 coronavirus. That NSBCC-funded project has proceeded well (with progress towards KRASG12D-specific inhibitors recently attracting additional investments). Further, we have also recently shown, using other funding, that the platform can be harnessed to selectively target antibiotic resistance pathogens using a variant of the PCC technology termed antibody-recruiting(AR) PCCs.4 Here we seek to combine the high-throughput aspect of PCC development that has been supported by the NCI,5 with the pathogen-targeting approach, to develop a series of precisely targeted inhibitors against SARS-CoV-2. This work has already been moving forward for the past few weeks, and is nearing the point where animal model work will soon be required.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
