EAGER: Carbon Dot-Based Transformative COVID-19 Therapy

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Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus (SARS-CoV-2). This disease is a critical problem that concerns everyone’s health and safety. As of July 15th, 2020, it has caused more than 580,000 deaths worldwide, and it is predicted to recur in the near future. At this time there is no cure to COVID-19 and traditional chemotherapy faces a series of challenges including: (1) the ability of SARS-CoV-2 to mutate readily; (2) ineffective antibodies; and (3) inadmissibility of most therapeutic agents across the blood-brain barrier. Consequently, this combination of factors gives SARS-CoV-2 an opportunity to hide in the brain, replicating and posing a lingering threat to the human body when its immune system becomes weak. Therefore, it is of great importance to come up with a treatment using the tools of biomedical engineering to prevent viral entry. In this project carbon dots, a class of novel nanoparticles that can cross the blood-brain barrier, will be utilized as versatile nanocarriers for various antibodies and an antiviral drug, remdesivir, that has been used to treat COVID-19. This method will make use of models comprised of specialized host cells and viruses to simulate the infection process of SARS-CoV-2. The outcomes of this project could lead to studies in which a great number of viral diseases can be treated with nanoparticles and therapeutic agents using the methodology introduced in this work. On the educational front, the project will provide training experiences for undergraduate and graduate students in a range of research methods, including surface chemistry, spectroscopy, nanomaterials, bioanalysis, nanocarriers, and bionanotechnology. Outreach activities include working with the media and TV to promote science and technology and participating with the Miami Frost Science Museum to curate exhibits and promote science to the general public. The goal of this research project is to design a novel biomedical system that applies carbon dots (CDs) as therapeutic nanocarriers. The carbon dots will be conjugated with antibodies of the spike proteins on SARS-CoV-2 (CD-NAbs), antibodies of the angiotensin-converting enzyme 2 (ACE2) receptors on host cells (CD-BAbs), and remdesivir. A novel disease model comprised of pseudohost cells and pseudoviruses will be developed used to analyze the inhibition effectiveness of the carbon dot conjugates. The effectiveness of separate and combined delivery of the carbon dot-antibody conjugates will be compared by measuring their IC50. The research idea is that CD-NAbs and CD-BAbs can respectively interact with the pseudoviruses and the pseudohost cells. The presence of carbon dot conjugates will reduce the binding of SARS-CoV-2 to the surface of host cells by steric effects and electrostatic repulsive forces. With the help of ACE2 BAbs, carbon dot conjugates will be able to deliver remdesivir into the infected cells to prevent viral replication. The results from this research project are expected to provide fundamental insights into whether and how long carbon dot conjugates will keep SARS-CoV-2 from infecting the host cells by reducing their available binding sites and inhibiting the approach of the virus to the cells.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.