HIS of SARS-CoV-2

Those data are for the manuscript "Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network". In those data, we studied the underlying mechanism of how SARS-CoV-2 interacts with its host. By comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.本数据集配套研究论文为《SARS-CoV-2的人同源序列通过NamiRNA-增强子网络上调透明质酸促进COVID-19临床进展》。本研究解析了SARS-CoV-2与宿主的相互作用机制：通过比对SARS-CoV-2与人类基因组序列，我们在SARS-CoV-2基因组中鉴定出5个完全保守的元件，将其命名为“人同源序列（human identical sequences, HIS）”；该类序列在SARS冠状病毒（SARS-CoV）与中东呼吸综合征冠状病毒（MERS-CoV）的基因组中亦存在同源序列，且SARS-CoV-2来源的HIS（HIS-SARS-CoV-2）在灵长类动物中高度保守。机制层面，HIS-SARS-CoV-2可作为病毒源性microRNA（miRNA），直接靶向人类基因组位点，并与宿主增强子相互作用，激活邻近及远端基因的表达，涵盖细胞因子基因、SARS-CoV-2经典细胞进入受体血管紧张素转换酶II（angiotensin converting enzyme II, ACE2），以及透明质酸合酶2（hyaluronan synthase 2, HAS2），进而促进透明质酸的生成。值得注意的是，COVID-19患者血浆透明质酸水平与疾病严重程度及急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）的发病风险显著相关，可作为COVID-19病情进展的预测标志物。HIS拮抗剂（HIS antagomirs）可有效下调血浆透明质酸水平；而4-甲基伞形酮（4-Methylumbelliferone, MU）作为透明质酸合成抑制剂，是缓解COVID-19患者肺部ARDS相关磨玻璃影的潜在治疗药物。本研究结果显示，SARS-CoV-2此前未被报道的HIS元件可诱导COVID-19患者发生细胞因子风暴与ARDS。因此，通过4-MU直接阻断HIS介导的激活通路或透明质酸合成，或可成为缓解COVID-19病情进展的有效策略。