The SARS-CoV-2 virus has caused a pandemic of profound global impact. Its high infectivity enabled it to spread rapidly across the world. In severe cases, infection with SARS-CoV-2 leads to respiratory failure, septic shock, and failure of vital organs, including the liver and kidneys. In the absence of an effective vaccine or therapeutic agent, reducing the population’s exposure to the virus is the only viable strategy for preventing infections and overburdening of the health care system. Transmission of SARS-CoV-2 occurs through multiple routes. Prevention of SARS-CoV-2 transmission requires effective and easy-to-use technologies directed against all modes of transmission. Funded by the Biomaterials Program in the Division of Materials Research of the Mathematical and Physical Sciences Directorate, and cofunded by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences of the Biological Sciences Directorate, this Rapid Response Research (RAPID) grant supports research into the development of biomimetic polymers that exploit the carbohydrate-binding properties of SARS-CoV-2 for virus immobilization. The developed polymers will be designed to produce virus-immobilizing gels and surfaces for applications in protective formulations and devices as well as functional studies, isolation, and purification of virions in scientific settings. The research serves the national interest by advancing the science of biomimetic materials and developing materials for the improvement of national health.
PART 2: TECHNICAL SUMMARY
The SARS-CoV-2 virus consists of single-stranded RNA that is enclosed in the nucleocapsid protein. This viral core is surrounded by a lipid membrane with three embedded proteins: the envelope protein, the membrane protein, and the spike (S) protein, which is responsible for binding to host cell receptors and host cell entry. The S protein has recently been shown to bind to the glycosaminoglycan (GAG) heparin. This project will integrate simulation, synthesis, and characterization in a forward- and backward-feeding loop approach to rationally design carbohydrate-conjugated polymers for immobilization of SARS-CoV-2 virions. Computer simulations will focus on defining the preferred GAG structures and topology of the S protein binding regions and will include structure modeling of the S protein, molecular docking of GAG oligosaccharides to the S protein, and molecular dynamics simulation of the co-complexes. Synthesis strategies toward GAG-conjugated polymers will include self-condensing ring-opening polymerization, self-condensing vinyl polymerization, and surface-initiated polymerization. Characterization and quantification of binding to the S-protein will be done by biolayer interferometry, surface plasmon resonance spectroscopy, and quartz crystal microgravimetry with dissipation monitoring.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
