Coronaviridae's 'Utility Belt': Identification, Characterization and Evolutionary Analysis of the Accessory Proteome of SARS-CoV-2 and other Coronaviruses

Despite the great efforts of international vaccination campaigns, the COVID-19 pandemic remains a major global health threat, as no antiviral drugs are available for severe COVID-19 patients, and the emergence of mutant viral strains risks to nullify vaccinations' efforts. SARS-CoV-2's genome has been found to encode for several strain-specific, non-essential accessory proteins with diverse functions. Some of these are known to be expressed from overlapping sequences within structural genes (e.g. 9b/9c within the Nucleocapsid (N) gene), but other overlapping sequences' potential for protein production remain unascertained. To identify new targets for drug development and help assess the threat variants pose to public health, it is crucial to identify these protein-coding sequences, study their products' functions and understand their origins. Our goals are to: Identify additional potential accessory genes encoded within SARS-CoV-2 N gene through in vitro translations and cell viability assays. Assess their role in in vitro infection models through generation of mutant SARS-CoV-2 strains. Dissect the dynamics of accessory gene birth/death in SARS-CoV-2 and related coronaviruses through phylogenetic analyses and dN/dS calculations. Test the hypothesis that coronaviruses adapt to changing host environments by acquiring/losing accessory genes by expressing a functional library of coronaviruses' accessory genes in multiple cell systems.