The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social, and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells. The S proteins from SARS and SARS-CoV-2 are similar, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-specific neutralizing antibodies to inhibit SARS-CoV-2. Here we used comparative pangenomic analysis of all sequenced reference Betacoronaviruses, complemented with functional and structural analyses. This analysis reveals that, among all core gene clusters present in these viruses, the envelope protein E shows a variant cluster shared by SARS and SARS-CoV-2 with two completely-conserved key functional features, namely an ion-channel, and a PDZ-binding motif (PBM). These features play a key role in the activation of the inflammasome causing the acute respiratory distress syndrome, the leading cause of death in SARS and SARS-CoV-2 infections. Together with functional pangenomic analysis, mutation tracking, and previous evidence, on E protein as a determinant of pathogenicity in SARS, we suggest E protein as an alternative therapeutic target to be considered for further studies to reduce complications of SARS-CoV-2 infections in COVID-19.

新型冠状病毒（SARS-CoV-2）的传播引发了全球性紧急情况，需要紧急解决方案进行检测和治疗，以防止对健康，社会和经济的影响不断升级。该病毒的刺突蛋白（S）能够与人类受体ACE2结合，因此成为预防病毒进入宿主细胞的疫苗的主要靶标。来自SARS和SARS-CoV-2的S蛋白相似，但是受体结合域（RBD）的结构差异使得无法使用SARS特异性中和抗体来抑制SARS-CoV-2。在这里，我们使用了所有测序参考的比较性全基因组分析冠状病毒，并辅以功能和结构分析。该分析表明，在这些病毒中存在的所有核心基因簇中，包膜蛋白E显示了SARS和SARS-CoV-2共有的变异簇，具有两个完全保守的关键功能特征，即离子通道和PDZ结合基序（PBM）。这些特征在引起急性呼吸窘迫综合征的炎性体的活化中起关键作用，所述炎性体是SARS和SARS-CoV-2感染的主要死亡原因。结合功能性蛋白质组学分析，突变追踪和以前的证据，我们认为E蛋白是SARS致病性的决定因素，我们建议将E蛋白作为替代治疗靶点，以进行进一步的研究以减少SARS-CoV-2感染的并发症。新型冠状病毒肺炎（COVID-19）：新冠肺炎（COVID-19）：COVID-19。