The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has become a global public health emergency. G-quadruplex, one of the non-canonical secondary structures, has shown potential antiviral values. However, little is known about the G-quadruplexes of the emerging SARS-CoV-2. Herein, we characterized the potential G-quadruplexes in both positive and negative-sense viral strands. The identified potential G-quadruplexes exhibited similar features to the G-quadruplexes detected in the human transcriptome. Within some bat- and pangolin-related betacoronaviruses, the G-tracts rather than the loops were under heightened selective constraints. We also found that the amino acid sequence similar to SUD (SARS-unique domain) was retained in SARS-CoV-2 but depleted in some other coronaviruses that can infect humans. Further analysis revealed that the amino acid residues related to the binding affinity of G-quadruplexes were conserved among 16,466 SARS-CoV-2 samples. Moreover, the dimer of the SUD-homology structure in SARS-CoV-2 displayed similar electrostatic potential patterns to the SUD dimer from SARS. Considering the potential value of G-quadruplexes to serve as targets in antiviral strategy, our fundamental research could provide new insights for the SARS-CoV-2 drug discovery.

由SARS-CoV-2（严重急性呼吸系统综合症冠状病毒2）引起的2019年冠状病毒病（COVID-19）大流行已成为全球公共卫生突发事件。G-四链体，一种非经典的二级结构，已显示出潜在的抗病毒价值。然而，关于新兴的SARS-CoV-2的G-四链体知之甚少。在这里，我们表征了正和负义病毒链中潜在的G-四链体。鉴定出的潜在G-四链体表现出与人类转录组中检测到的G-四链体相似的特征。在一些与蝙蝠和穿山甲相关的β冠状病毒中，G线而不是环在增强的选择性约束下。我们还发现，与SAD（SARS唯一域）相似的氨基酸序列保留在SARS-CoV-2中，但在其他一些可以感染人类的​​冠状病毒中却被消耗掉了。进一步的分析表明，在16,466个SARS-CoV-2样品中，与G-四链体的结合亲和力有关的氨基酸残基是保守的。此外，SARS-CoV-2中SUD同源结构的二聚体显示出与SARS的SUD二聚体相似的静电势模式。考虑到G-四链体在抗病毒策略中的潜在价值，我们的基础研究可以为SARS-CoV-2药物发现提供新的见解。SARS-CoV-2中SUD同源结构的二聚体显示出与SARS的SUD二聚体相似的静电势模式。考虑到G-四链体在抗病毒策略中的潜在价值，我们的基础研究可以为SARS-CoV-2药物发现提供新的见解。SARS-CoV-2中SUD同源结构的二聚体显示出与SARS的SUD二聚体相似的静电势模式。考虑到G-四链体在抗病毒策略中的潜在价值，我们的基础研究可以为SARS-CoV-2药物发现提供新的见解。