This $1,000,000 Cooperative Agreement awarded by the National Science Foundation (NSF) under the Technology, Innovation, and Partnerships (TIP) program (CFDA 47.084) supports research and development efforts by Akanocure Pharmaceuticals Inc. to optimize a novel, broad-spectrum antiviral and immunomodulatory agent for oral administration against coronaviruses. The project focuses on lead optimization, including the design, synthesis, and testing of analogs with improved drug-like properties for...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $899,935 to the Scripps Research Institute to identify novel B cell epitopes on the SARS-CoV-2 spike protein and other human coronaviruses. The goal is to uncover broadly neutralizing antibody epitopes that can inform the design of next-generation COVID-19 vaccines and therapeutics, enhancing pandemic preparedness. The...
This $15,981,588 project grant from the National Institutes of Health's National Institute of Allergy and Infectious Diseases aims to develop pan-coronavirus vaccines. Led by Washington University, the collaborative program includes eleven laboratories seeking to design optimized B and T cell antigens conferring broad immunity against sarbecoviruses and merbecoviruses. The three-year award beginning September 2022 supports three integrated research projects and two centralized cores. Project 1...
Phenotarget Biosciences Inc. was awarded a $255,473 Project Grant from the National Science Foundation Division of Industrial Innovation under the Engineering (47.041) federal grant program. The grant supports discovery and development of macrocyclic peptide inhibitors of SARS-CoV-2 spike protein for the treatment of COVID-19 from July 1, 2021 through March 31, 2022. The Engineering program seeks to improve quality of life and economic strength by fostering innovation and excellence in...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) provides $380,320 to the Trustees of the University of Pennsylvania, doing business as the Clinical Practices of the University of Pennsylvania, to conduct research on elucidating the lineage dynamics of optimal human CD8 T cell responses to SARS-CoV-2 and how CD8 T cell homeostasis is altered in Long COVID. The research aims to define human memory...
This Project Grant award from the Department of the Army Medical Command's Military Medical Research and Development program (CFDA 12.420) provides $2,076,014 to Stanford University for research titled "Repurposing of Pan-ERBB Inhibitors to Protect from Coronaviral Infection, Inflammation, and Lung Injury." The award period is from September 30, 2022 to September 29, 2026. Under the award, Stanford University will conduct research to determine the therapeutic potential of pan-ERBB...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $243,713.00 to the University of Massachusetts Medical School to conduct comprehensive research on the evolution of drug resistance in SARS-CoV-2. The project aims to systematically investigate the interdependence of mutations that disrupt drug binding and those that increase enzyme activity, which are typically...
This $131,988 Project Grant from the National Heart, Lung and Blood Institute, part of the Department of Health and Human Services, supports research targeting determinants of SARS-CoV-2 host interaction in airways. Funded through the Cardiovascular Diseases Research program, the grant aims to identify master regulator proteins that mechanistically regulate SARS-CoV-2 interactions in the airways. Using organotypic airway epithelial culture and systems biology tools at Columbia University, the...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded Oklahoma State University a Project Grant under the Allergy and Infectious Diseases Research federal grant program (CFDA 93.855) to develop a synthetic miR-7702 as a potential therapeutic for SARS-CoV-2 infection. The $411,400 award, granted on July 10, 2025, will support research to delineate the mechanism by which miR-7702 inhibits SARS-CoV-2 replication and evaluate the in vivo toxicity, biodistribution, and therapeutic...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $116,022 Project Grant under CFDA 93.855 - Allergy and Infectious Diseases Research to The University of Texas Health Science Center at San Antonio (UTHSCSA) to conduct studies on the SARS-CoV-2 main protease (Mpro) dimerization mechanism. The key objectives of this grant are to: Use quantitative luciferase-based reporter assays developed by the researchers to study the Mpro dimerization mechanism and identify...
DEVELOPMENT OF HOST- ORIENTED THERAPEUTICS TARGETING SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2), - THE ULTIMATE GOAL OF THIS PHASE I APPLICATION IS TO DISCOVER AND DEVELOP HOST-ORIENTED SMALL MOLECULE COMPOUNDS TARGETING SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION. SARS-COV-2 IS A NOVEL CORONAVIRUS DRIVING THE CURRENT GLOBAL PANDEMIC OF SEVERE RESPIRATORY SYNDROME IN HUMANS. ANTIVIRAL THERAPEUTICS ARE URGENTLY NEEDED TO COMBAT INFECTION BY SARS-COV-2 AND NEW VARIANTS THAT ARE CONTINUING TO EMERGE. WE HAVE DISCOVERED SEVERAL CHEMICAL SERIES THAT TARGET MODULAR INTERACTIONS BETWEEN SPECIFIC HOST PROTEINS CONTAINING WW-DOMAINS (E.G. NEDD4) AND VIRAL PROTEINS CONTAINING PPXY MOTIFS (E.G. EBOLA VP40). NOTABLY, EMERGING RNA VIRUS PATHOGENS SUCH AS EBOLA, MARBURG, LASSA, AND RABIES VIRUSES ALL ENCODE PPXY MOTIFS THAT RECRUIT HOST WW-DOMAIN CONTAINING PROTEINS TO FACILITATE EFFICIENT VIRUS EGRESS, SPREAD, AND TRANSMISSION. INTERESTINGLY, THE SURFACE-EXPOSED SPIKE GLYCOPROTEIN (S) OF SARS-COV-2 ALSO HAS A PUTATIVE WW-DOMAIN BINDING MOTIF (25PPAY28), THAT IS NOT PRESENT IN THE S PROTEIN OF SARS-COV-1 OR MORE ATTENUATED CORONAVIRUS STRAINS. THE ACQUISITION OF THIS PPAY MOTIF IN THE MAJOR SURFACE PROTEIN OF SARS-COV-2 VIRIONS RAISES THE INTRIGUING POSSIBILITY THAT IT MAY CONTRIBUTE TO THE UNIQUE PATHOGENICITY AND/OR TRANSMISSION OF SARS-COV-2 VIA INTERACTIONS WITH SPECIFIC HOST WW-DOMAIN BEARING PROTEINS. IN OUR ONGOING STUDIES ON FILOVIRUSES AND ARENAVIRUSES, WE HAVE USED EXTENSIVE SAR TO IDENTIFY A LEAD COMPOUND SERIES CAPABLE OF BLOCKING EGRESS AND SPREAD OF LIVE EBOV, MARV, AND LAFV IN CELL CULTURE, AS WELL AS BLOCKING DISEASE PROGRESSION IN VIVO IN A LIVE MARV CHALLENGE MODEL. HERE, WE HYPOTHESIZE THAT "INFORMED" SAR ANALYSES OF OUR IN-HAND PPXY/WW-DOMAIN INHIBITORS (E.G. LEAD CANDIDATE FC-10696) WILL LEAD TO THE DISCOVERY OF ANALOGS CAPABLE OF BLOCKING EGRESS AND DISEASE PROGRESSION OF SARS-COV-2, AS WELL AS RELATED PPXY-CONTAINING VARIANTS THAT MAY EMERGE IN THE FUTURE. IN SUPPORT OF OUR HYPOTHESIS, WE PRESENT STRONG PRELIMINARY DATA SHOWING THAT THE PPXY MOTIF WITHIN THE S PROTEIN OF SARS-COV-2 VIRUS CAN INTERACT WITH HOST WW-DOMAIN CONTAINING PROTEINS THAT ARE KNOWN TO PROMOTE EGRESS AND SPREAD OF EBOV, MARV, AND LAFV. MOREOVER, OUR CURRENT LEAD CANDIDATE PPXY BUDDING INHIBITORS SHOW ACTIVITY IN BLOCKING EGRESS OF LIVE SARS-COV-2 VIRUS INFECTION IN HUMAN LUNG EPITHELIAL CELLS. IN THIS PHASE I PROPOSAL, WE WILL IDENTIFY AND EVALUATE HOST-ORIENTED INHIBITORS AS POTENTIAL THERAPEUTICS FOR SARS-COV-2 AND RELATED CORONAVIRUSES BY COMBINING THE PHARMACEUTICAL AND MEDICINAL CHEMISTRY EXPERTISE OF THE SCIENTISTS AT THE FOX CHASE CHEMICAL DIVERSITY CENTER, INC. (FCCDC) WITH THE EXPERTISE AND EXPERIENCE OF THE HARTY LAB AT THE UNIVERSITY OF PENNSYLVANIA IN THE EXPERIMENTAL ASPECTS OF VIRUS-HOST INTERACTIONS AND ANTIVIRAL THERAPY, AND THE LAB OF OLENA SHTANKO AT TEXAS BIOMEDICAL RESEARCH INSTITUTE FOR EVALUATING COMPOUNDS AGAINST LIVE VIRUSES UNDER BSL-3 CONDITIONS. THE THREE AIMS ARE (1) LEAD FINDING AND OPTIMIZATION MEDICINAL CHEMISTRY INCLUDING ADME PROFILING, (2) EVALUATION FOR THE ABILITY TO SPECIFICALLY INHIBIT EGRESS OF SARS-COV-2 VLPS AND PPXY- MEDIATED S-HOST PROTEIN INTERACTIONS, AND (3) IN VITRO AND IN VIVO ANALYSES AGAINST AUTHENTIC SARS-COV-2 VIRUS.