5' UTR barcode of the 2019 novel Coronavirus leads to insights into its virulence

ABSTRACT

"Novel coronavirus 2019" (which was renamed subsequently "severe acute respiratory syndrome coronavirus-2" (SARS-CoV-2) on 11 February 2020) caused a pneumonia outbreak in Wuhan (Hubei Province, China) in December 2019. In our previous studies, two important findings regarding SARS-CoV-2 were reported, for the first time, on 21 January 2020 (1) multiple alternative translations of a coding sequence in genomes of betacoronavirus subgroup B;(2) a novel mutation in the spike (S) proteins of betacoronavirus. By this mutation, SARS-CoV-2 acquired a cleavage site for the furin enzyme in its S protein, which is not present in the S proteins of most other betacoronaviruses (e.g. SARS-CoV). In the present study, we performed analyses of 5' untranslated regions (UTRs) in betacoronavirus. Using 5' UTR barcodes, 1,265 betacoronaviruses were clustered into four classes, and viruses in each class had similar virulence. The class 1, 2, 3 and 4 match the subgroup C, B, A and D of betacoronavirus, respectively. In particular, SARS-CoV-2 and SARS-CoV have the same 5' UTR barcode. As the main contribution of the present study, we developed 5' UTR barcoding to be used in the detection, identification, classification and phylogenetic analysis of, but not limited to coronavirus. Our method is very useful for early-warning, prevention and control of coronavirus. We found that Internal Ribosome Entry Sites (IRESs) may have important roles in the virulence of betacoronavirus. This important finding is reported, for the first time, to understand the virulence of SARS-CoV-2 at the molecular level. This finding can be used directly for vaccine development and design of drugs against SARS-CoV-2, but such development is not limited to coronavirus only. In addition, we propose that the upstream hairpin structures neighboring the start codons in mRNAs have important roles in protein translation in eukaryotes.