The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G₂N_xG₂N_yG₂N_zG₂) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.

中文翻译：

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SARS-CoV-2 中 G-四链体形成序列的发现


由新型冠状病毒 SARS-CoV-2 引起的疫情已被宣布为全球卫生紧急事件。长期以来，基因组中的 G 四链体结构一直被认为对于调节多种生物体中的许多生物过程至关重要。我们分析并鉴定了 SARS-CoV-2 RNA 基因组中的 25 个四个连续 GG 序列 (G ₂ N _x G ₂ N _y G ₂ N _z G ₂ )，这表明了假定的 G 四联体形成序列 (PQS)。对 SARS-CoV-2 PQS 的详细分析揭示了它们在 ORF1 ab、spike (S)、ORF3a、membrane (M) 和 nucleocapsid (N) 基因开放阅读框中的位置。在冠状病毒科的其他成员中也发现了相同的 PQS。通过多次光谱测定，证实位于 13385 和 24268 位的顶级 PQS在体外形成 RNA G 四链体结构。此外，它们与病毒解旋酶（nsp13）的直接相互作用是通过微尺度热泳确定的。分子对接模型表明，nsp13 通过允许鸟嘌呤碱基翻转远离鸟嘌呤四联体平面来扭曲 G-四联体结构。靶向病毒解旋酶和 G-四链体结构是潜在抑制 SARS-CoV-2 病毒的一种有吸引力的方法。