The COVID-19 pandemic is caused by the SARS-CoV-2 virus, a virus whose structure has not been fully characterized. The spike protein of the virus is believed to play a key role in infection. In this work computer simulations will be used to understand the role of sugar molecules that normally are present on the outside of host cells on the binding to host cells and the infectivity of the virus. Simulations will examine host cell membranes from species that include humans, cats, ferrets and other non-human primates in order to better understand the differences between virus transmission in different species. These simulations will provide information that is not currently accessible through experiment. The simulations and data sharing capabilities developed in this work will improve responsiveness against future pandemics. Additionally, the project will provide a training for two postdoctoral fellows.
This research will use MD (molecular dynamics) computational methodology together with experimental data, to build and simulate biologically realistic conditions for the SARS-CoV-2 virus spike protein, alone, and also in complex with various forms of the ACE2 receptor and host cell membrane components. The aim is to determine areas of spike protein vulnerabilities as well as understand the effects of glycosylation on the structure and function of the SARS-CoV-2 infection machinery. The simulations will include ACE2 receptors in cats, ferrets, and other nonhuman primates to understand the molecular underpinnings of virus host range and transmissibility. The proposed research will provide a more complete understanding of the SARS-CoV-2 infection machinery and the molecular constituents with which it interacts at different host cells.
This RAPID award is made by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.
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.