RAPID: Comparative functional characterization of strain-specific CoV E-proteins and involvement in host-specific virulence

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Viral infections in the last decades with different strains of the coronavirus (CoV) have led to the SARS-CoV (2003) and MERS (2012) epidemics and to the most recent COVID-19 pandemic (2019). At this point, no vaccine or effective antiviral drug is commercially available for these human pathogens. CoVs are built out of four major structural proteins; the nucleocapsid (N) protein engulfing the viral RNA, the spike (S) protein, the membrane (M) protein and the envelope (E) protein. Presently, academic and pharmaceutical efforts are mainly focused on the S-protein which is involved in the entry of the virus into the host cell, whereas the M- and E-proteins are less well studied but are shown to be involved in viral replication. This project will study the E-protein from different CoV strains to better understand its function. This project will improve our understanding of SARS-CoV-2, and this understanding is knowledge necessary to identify new therapeutics to control this current COVI-19 pandemic. In addition to increasing knowledge about SARS-CoV-2 biology, this project also supports the training of a post-doctoral fellow, broadening participation in STEM. This project will study the E-protein of SARS-CoV-2 and other coronaviruses (CoVs) to understand the role of this ion channel in host-virion interaction. A multi-level approach will be used to gain comprehensive understanding on effects of the post-translational modifications and sequence variability of various E-proteins from different CoV strains. Patterns in the post-translational modification of E-proteins will be identified to determine whether these modifications affect the functionality of the E-protein in model membranes. Using model membranes allows for control of key-features in the membrane environment, namely charge of lipid head-groups and saturation of fatty acids creating a microdomain or non-microdomain environment. The throughput of these recordings will be increased by using our unique abilities to combine modern electronics and membrane biophysics. E-proteins from different CoV strains will be used to identify the impact on the development of productive or non-productive infections in a host-like environment. The current COVID-19 public health emergency makes understanding this new pathogen of urgent importance. Little is known about this novel CoV and its relationship to other CoV virions. Understanding better the exact role that the E-protein plays in the host-virion interaction will be very helpful in devising new therapeutics. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, 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.