Rensselaer Professor Jonathan Dordick and collaborators from Rensselaer Polytechnic Institute and Albany Medical College have been awarded $500,000 from the New York State Biodefense Commercialization Fund to engage in research for the development of a Pentosan Polysulfate (PPS)-based nasal spray to block COVID-19.

“Despite advances in both therapeutics and vaccines for COVID-19, there remains a critical need to develop a simple, easy to use, and highly effective prophylactic to prevent transmission and serious illness as a result of infection with SARS-CoV-2,” said Dr. Dordick, Institute Professor of Chemical/Biological Engineering at Rensselaer, and co-director of the Heparin Applied Research Center (HARC). “Since the virus uses the nasal passages as a first line of infection, an ideal approach is to use a safe and effective nasal spray. We have shown that pentosan polysulfate (PPS), an FDA-approved drug for an entirely different indication, shows very strong binding to SARS-CoV-2, thereby neutralizing the virus. Our goal now is to incorporate PPS into a nasal spray formulation to block SARS-CoV-2 infection either pre- or post-exposure. Moreover, a similar mechanism of infection is used by a number of viruses, including other coronaviruses and some common cold viruses, and thus the PPS-based nasal spray could be useful against other respiratory infections.”

Dr. Dordick is the Principal Investigator (PI) of the project and will lead the research. He has expertise in human cell culture and high-throughput screening, SARS-CoV-2 pseudovirus preparation and screening, drug discovery and toxicology. He has founded four companies, including three in drug discovery and he will be responsible for project oversight. The research team leadership also includes Dr. Robert Linhardt, Constellation Chair at Rensselaer, Department of Chemistry/Chemical Biology, and Co-Director of HARC, and Dr. Dennis Metzger, Department of Immunology and Microbial Disease, Albany Medical College. Dr. Linhardt is an expert in pharmaceutical chemistry, glycobiology, and sulfated polysaccharides, and will be responsible for PPS chemistry and formulation. Dr. Metzger will be responsible for in vitro and in vivo studies with patient-derived SARS-CoV-2 strains.

Despite the success of vaccines to prevent COVID-19 infection and reduce severity of breakthrough infections, there remains a notable resistance to vaccination, and waning immunity offered by vaccines against emerging variants may necessitate new generations of vaccines. There has been success in advancing therapeutics, such as dexamethasone, remdesivir, molnupiravir, paxlovid, and monoclonal antibodies. None of the vaccines and therapeutics provide for a combined prophylactic/early-stage therapeutic that can be administered at home and is broadly applicable to other respiratory infections. Therefore, new agents are urgently needed for prophylaxis/early-stage treatment of COVID-19.

Home or physician’s office use is expected to have a high degree of public acceptance and will help to address outbreaks of COVID-19, particularly as new variants emerge and we enter the endemic phase of the disease. A prophylactic nasal spray to prevent COVID-19 infection could be used pre- or post-exposure, and could be used daily by persons who are unable to be vaccinated due to medical reasons. Individuals in healthcare, transportation, food services are particularly vulnerable to SARS-CoV-2 and would benefit from use of a prophylactic nasal spray. We expect the PPS nasal spray to be useful against future infectious disease threats and the impact of the spray is likely to extend well beyond the current COVID-19 pandemic.

“This important work at the interface of life sciences and engineering by Dr. Dordick and his team truly embodies Rensselaer’s founding mission – ‘application of science to common purposes of life’ – and will have great impact on human health,” said Shekhar Garde, Dean of the School of Engineering at Rensselaer.  

Other collaborators include:

Co-Investigator Dr. Adolfo Jaitovich, Associate. Professor of Pulmonary Critical Care and Molecular and Cellular Physiology at AMC. He is a physician-scientist with both clinical duties and an active translational research-based program in pulmonary critical care and molecular signatures of COVID-19 infection.

Co-Investigator: Dr. Fuming Zhang, Research Professor of Chemical and Biological Engineering and Chemistry and Chemical Biology at Rensselaer. Dr. Zhang has expertise in measuring molecular interactions of proteins and polysaccharides using surface plasmon resonance.

Co-Investigator: Dr. Ke Xia, Research Scientist, Department of Chemistry and Chemical Biology at Rensselaer. Dr. Xia’s expertise is in analytical chemistry and mass spectrometry, and pharmacokinetic analysis of complex polysaccharide drugs, such as PPS.

The New York State Biodefense Commercialization Fund was created to accelerate the development and commercialization of life science innovations that address serious infectious disease threats including COVID-19 and its variants, while also creating jobs and encouraging continued growth across New York’s expanding life science industry.