Understanding the Lipid-dependent function of SARS-CoV-2 E Protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for COVID-19, a disease which has resulted in the death of millions worldwide. COVID-19 ranges in severity of symptoms which are related to the inflammatory response. Although the field has progressed significantly, there is still a critical gap in understanding virus-host lipid interactions that contribute to viral assembly and budding of this lipid-enveloped virus. There are four structural proteins encoded in the SARS-CoV-2 genome: membrane, envelope (E), nucleocapsid, and spike. These proteins give shape to the bilayer lipid coat that encapsulate the genomic core necessary for virus infection and replication. These proteins are essential for viral reproduction but how they interact with each other and how lipid species regulate their assembly is not well understood. It is established that inflammation is common during infection. One enzyme that participates in this process is ceramide kinase (CERK), which synthesizes the pro-inflammatory lipid, ceramide-1-phosphate (C1P). CERK is in fact a therapeutic target for a variety of inflammatory disorders. My primary goal is to define the relationship between CERK activity and SARS-CoV-2 assembly. We aim to understand the impact that CERK activity has on the localization and assembly of SARS-CoV-2 structural proteins. I am interested in how CERK regulates E protein localization and formation of virus-like particles and the process by which E-lipid interactions contributes to membrane curvature changes necessary for formation of new viral particles. Overall, I anticipate that this study will help define the relationships between a host enzyme and host membranes and the assembly of SARS-CoV-2.