Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities. Our analyses suggest the presence of unique sequence signatures in the 3′ untranslated region (3′-UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2 and SARS-CoV as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host-microRNA-mediated interaction between the 3′-UTR and human microRNA hsa-miR-1307-3p based on the results of multiple computational target prediction analyses and an assessment of similar interactions involving the influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3′-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection and the exploitation of conserved features in the 3′-UTR as therapeutic targets warrant further investigation.

中文翻译：

---

SARS-CoV-2 的保守基因组末端作为共同进化的功能元件和潜在的治疗靶点

截至 2020 年 10 月，严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 已感染全球超过 4000 万人，超过 100 万人死亡，抗病毒药物和疫苗的开发和测试正在进行中。为了深入了解 SARS-CoV-2 的进化和药物靶点，我们研究了 SARS-CoV-2 基因组序列与其他已充分表征的人类和动物冠状病毒基因组序列的差异以及差异程度，以及多态性如何SARS-CoV-2 基因组通常是。我们最终试图确定 SARS-CoV-2 基因组中可能有助于其病毒复制、宿主致病性和脆弱性的特征。我们的分析表明，β 冠状病毒 B 谱系的 3′ 非翻译区 (3′-UTR) 中存在独特的序列特征，该谱系在系统发育上包含 SARS-CoV-2 和 SARS-CoV 以及多组蝙蝠和动物冠状病毒。此外，我们还确定了不同 SARS-CoV-2 毒株的全基因组变异模式，这可能反映了选择的影响。最后，我们根据多个计算目标预测分析的结果以及对涉及甲型流感的类似相互作用的评估，为 3'-UTR 和人类 microRNA hsa-miR-1307-3p 之间可能存在宿主 microRNA 介导的相互作用提供证据H1N1 病毒。这种相互作用还表明了一种可能的生存机制，即 SARS-CoV-2 3'-UTR 的突变导致宿主免疫反应减弱。宿主 microRNA 在 SARS-CoV-2 复制和感染中的潜在作用以及利用 3'-UTR 中的保守特征作为治疗靶点值得进一步研究。