Determining the role of 90K on SARS-CoV-2

Project Summary/Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus that is responsible for the current pandemic that is plaguing the world and has resulted in millions of dead. Due to the recent emergence of this viral pathogen, there is a dearth of information regarding SARS-CoV-2 infection and the role of cellular host factors associated with it. A better understanding of SARS-CoV-2 infection and the host factors involved with it is necessary for the development of SARS-CoV-2-directed therapeutics. A factor that has been associated with antiviral activity, yet its antiviral mechanism is not elucidated is galectin-3-binding-protein (LGALS3BP/90K). 90K is a secreted glycoprotein that is upregulated during viral infections and is an interferon stimulated gene. Despite the fact that 90K is an interferon stimulated gene, very little is known about its contribution to the antiviral defense of the cell. It is suggested that 90K affects human immunodeficiency virus (HIV) virion biogenesis in a process that is not yet elucidated. Moreover, the antiviral role of 90K has never been studied in other virus families outside of retroviruses. This proposal investigates the role of 90K on SARS-CoV- 2 infection. The goal of this proposal is to provide mechanistic evidence on the effect of 90K during SARS-CoV- 2 infection. Furthermore, many host genes that target viral infections are antagonized by virally encoded genes. There are currently no viral genes known to counteract 90K. SARS-CoV-2 encodes a number of viral accessory proteins, whose function is largely unknown. Therefore, another aspect of this proposal is to identify the mechanism by which SARS-CoV-2 accessory proteins counteract 90K. This study will elucidate the role of 90K during SARS-CoV-2 infections, as a better understanding of host cellular factors that target SARS-CoV-2 is needed and will provide novel valuable information regarding the role of SARS-CoV-2 encoded genes. In conclusion, the identification of host genes that target SARS-CoV-2 infection and their viral antagonists provide possible new targets for the development of SARS-CoV-2 pharmaceutical treatments.