Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Rahaman, Jordon; Siltberg-Liberles, Jessica

SARS-CoV and MERS-CoV are positive (+)-strand RNA viruses encoding approximately 25 protein products. The MERS-CoV proteome is primarily composed of two polyproteins, ORF1a and ORF1ab; the latter is generated by a -1 ribosomal slippage frameshift. These proteins are cleaved into 16 nonstructural proteins (NSPs). NSPs 1-10 are products of both polyproteins, whereas NSPs 12-16 are only yielded by ORF1ab. NSP11 is unique to ORF1a ( van Boheemen et al. 2012) . Structural proteins envelope (E), spike (S), membrane (M), and nucleocapsid (N) are elements of the physical structure that encloses the viral genome and come from distinct reading frames, unlike ORF1a and ORF1ab, which come from overlapping reading frames. Additionally, the structural proteins are the product of subgenomic mRNAs that are joined during discontinuous negative RNA strand synthesis (van Boheemen et al. 2012) . Finally, NS3 protein (NS3), NS4A protein (NS4A), NS4B protein (NS4B), NS5 protein (NS5), and Orf8b protein encompass the remainder of the proteome and also arise from distinct reading frames (van Boheemen et al. 2012) .