Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Jacob Kames; David Dillon Holcomb; Ofer Kimchi; Michael DiCuccio; Nobuko Hamasaki-Katagiri; Tony Wang; Anton A Komar; Aikaterini Alexaki; Chava Kimchi-Sarfaty

Coronaviruses (CoVs) are enveloped, positive-stranded RNA viruses with a large genome of about 30 kb encoding multiple proteins [10] . Translation of a positive-stranded RNA from the initial infectious virus particles generates (among other proteins) a virally encoded RNA dependent RNA polymerase (replicase). This replicase is necessary for viral replication and subsequent generation of . CC-BY 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.30.016832 doi: bioRxiv preprint viral subgenomic RNAs (sgRNAs), from which the synthesis of structural and accessory proteins occurs [10] . ORF1ab, which encodes the replicase polyprotein (among other proteins) occupies about two thirds of the 5' prime end of this genome [10, 11] . A -1 programmed ribosomal frameshift (PRF) occurs half-way through ORF1ab, allowing the translation of ORF1b [10] . The efficiency of the frameshift thus modulates the relative ratios of proteins encoded by ORF1b and the upstream ORF1a and is critical for coronavirus propagation. Frameshift efficiency (ranging from 15 to 60%) in -1 PRFs is commonly regulated by pseudoknotted mRNA structures following the frameshift, and the conservation of a threestem pseudoknot in coronaviruses has been previously characterized [12] . Following ORF1ab, are the spike (S), ORF3a, envelope (E), membrane (M), ORF6, ORF7a, ORF7b, ORF8, nucleocapsid (N) and ORF10 genes. S, E, M and N are the structural proteins of the virus [11] . S promotes attachment and fusion to the host cell, during infection [13] . In the case of SARS-CoV-2, S binds to the human angiotensinconverting enzyme 2 (ACE2) [11, 14, 15] . The E protein is an ion channel and regulates virion assembly [16] . The M protein also participates in virus assembly and in the biosynthesis of new virus particles [17] , while the N protein forms the ribonucleoprotein complex with the virus RNA [18] and has several functions, such as enhancing transcription of the viral genome and interacting with the viral membrane protein during virion assembly [19] . Many of the other ORFs have unknown functions or are not well characterized [20] , as their presence is not consistent across all coronaviruses.