Functional pangenome analysis provides insights into the origin, function and pathways to therapy of SARS-CoV-2 coronavirus

Abstract

Background: Recent epidemic of novel coronavirus (SARS-CoV-2) has triggered a rising global health emergency that demands urgent analysis of its genome and solutions for detection and therapy. Methods: We used a comparative pangenomic analysis of Betacoronavirus sequenced thus far to detect the core and accessory gene clusters of this genus including SARS-CoV-2. We then annotate the functions, which are confirmed by structural analysis, and predict the potential location within the host cells of these proteins. Findings: We found five accessory gene clusters common to the SARS clade, including SARS-CoV-2, that perform functions supporting their pathogenicity. Phylogenetic analysis showed one of the accessory gene clusters, the protein E, to be present across the inferred evolutionary pathway of the SARS clade, including that of the horseshoe bat virus (Hp-betacoronavirus/Zhejiang2013), inferred to be the parental member of the clade. The E protein is highly conserved in the clade, differing between SARS and SARS-Cov2 with a difference of single amino acid substitution and a single amino acid insertion present in SARS but absent from SARS-CoV-2. Betacoronavirus pangenomedb is available at http://pangenomedb.cbrc.kaust.edu.sa. Interpretation: The characterization and functional assessment of SARS-CoV-2 envelope, E, protein in gene cluster 6, together with previous findings on this protein for SARS, leads us to recommend that detection of COVID-2019 be developed based on the SARS-CoV-2 E protein and that treatment using mutated SARS-Cov-2 lacking the E protein be explored as a promising candidate for a vaccine.