Elucidating the role of SERINC5 in SARS-CoV-2 infection

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A viral pathogen associated with severe pneumonia was recently identified as the cause of a global pandemic that has resulted in the death of over two million people. This viral pathogen was later classified as a coronavirus that was subsequently named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Currently, there is a paucity of information regarding SARS-CoV-2 infection and the cellular factors associated with it. The identification of host factors that target SARS-CoV-2 infection and the elucidation of their mechanism of action is critical for the development of SARS-CoV-2 therapeutics. It was recently shown that the Serine Incorporator (SERINC) protein family, which is comprised by 5 multipass transmembrane proteins (SERINC1-5) plays a critical role in retroviral entry, yet the role of SERINC factors on other viral infections including SARS-CoV-2 infection is currently unknown. This proposal investigates the effect of SERINC5 on SARS-CoV-2 infection. The goal of this proposal is to provide mechanistic evidence on the effect of SERINC5 on SARS-CoV-2 entry, as many times, host factors use different mechanisms to restrict viruses that belong to different viral families. Previous research has shown that human immunodeficiency virus (HIV) is potently restricted by SERINC5 in a mechanism that has not been fully elucidated. However, HIV encodes an accessory protein, Nef, which counteracts the deleterious effect of SERINC5. Similar viral proteins have been identified in other retroviruses, which demonstrates the importance of SERINC5 in retrovirus infection. Hence another aspect of this proposal is to determine a SARS-CoV-2 encoded factor that targets SERINC5 and the mechanism it utilizes to counteract SERINC5. This study will provide much needed insight into the role of a novel host factor that targets SARS- CoV-2, which is of great importance as there is not a lot of mechanistic understanding of host factors that target SARS-CoV-2. Moreover, little is known about the role of SARS-CoV-2 proteins and how they modulate the host cell; hence, the findings of this proposal will provide valuable information regarding the function of SARS-CoV-2 encoded factors. Finally, the discovery of host factors that restrict SARS-CoV-2 infection may expand the gamut of potential drug targets for the development of SARS-CoV-2 antivirals.