Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling

Lin Lv; Xiaoqing Xie; Qiyu Gong; Ru Feng; Xiaokui Guo; Bing Su; Lei Chen

The transcriptome of the virus is a fundamental aspect of its biology. For We developed an informatics pipeline to infer sgRNA profiles from these short reads samples. In short, 73 reads were first aligned to a combined reference of human (hg38) and either SARS-CoV-2 (GeneBank ID 74 It's followed by ORF7a, M, ORF3a and S, all just above 10%. E is the lowest of the eight at about 1%. All of 84 them also have TRS except E. The break point for these ORFs were situated between 9 to 146 nt upstream 85 of the ORF start, and have no start codon (ATG) in-between. ORF7b and ORF10 are two ORFs that were 86 supported in a recent proteomics study on SARS-CoV-2. However, we did not see supporting break 87 points/sgRNA in our first scan-through. We then looked extra hard by lowing our threshold. The few extra 88 break points emerged were still very far away from those ORF start or has out-of-frame start codon between 89 the break point and the ORF start. Thus ORF7b and ORF10 were not supported by our data, this could be 90 1.6% and 1.25% respectively. We notice this difference is in accordance with the three's capability to spread 122 among hosts: MERS being the most deadly, has a R0 of 0.69, SARS-CoV-2 having the lowest fatality rate, 123 spread very rapidly and SARS comes in between in terms of both transmissibility and fatality rate [10-12]. 124 SARS-CoV-2 and SARS-CoV both use ACE2 as the receptor for celluar invasion. Cryo-EM study suggested 125 that the SARS-CoV-2 has higher binding affinity to ACE2 [13]. Our study suggest yet another possibility. The 126 elevated S expression, may make an average SARS-COV-2 having more Spikes on surface or just assemble 127 more efficiently. 128