Potential G-quadruplexes and i-Motifs in the SARS-CoV-2.
Potential G-quadruplexes and i-Motifs in the SARS-CoV-2.
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DOI：
10.1371/journal.pone.0250654
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Bañobre-López M
中科院分区：
文献类型：
--
作者：
Belmonte-Reche E;Serrano-Chacón I;Gonzalez C;Gallo J;Bañobre-López M
四链体结构已在多种生物体中被发现，它们在分子过程的调节中发挥重要作用，因此被提议作为许多疾病的治疗靶点。在本文中，我们报告了使用开源算法 G4-iM Grinder 的升级版本对 SARS-CoV-2 基因组和相关病毒进行的广泛生物信息分析。该版本改进了软件的功能，包括一种简单的方法来确定受所发现的候选者影响的潜在生物特征。该算法的四链体定义针对 SARS-CoV-2 进行了优化。使用宽松的四联体定义规则集（除了其他参数外还接受两个残基 G 轨道和 C 轨道），发现了 512 个潜在的四联体候选者。这些序列通过它们的体外形成概率、它们在病毒RNA中的位置、它们的独特性和它们的保存率进行评估（在超过17000个不同的COVID-19临床病例中计算，并在持续大流行期间的不同时间和地点进行测序）。随后将这些结果与其他冠状病毒科成员、其他 IV 组 (+)ssRNA 病毒和整个病毒领域进行比较。进一步分析和表征了与其他病毒物种共有的序列。研究了 SARS-CoV-2 特有的高分序列，以调查相似物种之间的差异。然后通过实验证实了最佳候选物的四链体形成。使用 NMR 和 CD 光谱，我们发现了几种高度稳定的 RNA 四链体，可能是 SARS-CoV-2 的合适治疗靶点。
Quadruplex structures have been identified in a plethora of organisms where they play important functions in the regulation of molecular processes, and hence have been proposed as therapeutic targets for many diseases. In this paper we report the extensive bioinformatic analysis of the SARS-CoV-2 genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for SARS-CoV-2. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, 512 potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over seventeen thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were then compared subsequently to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire viral realm. Sequences found in common with other viral species were further analyzed and characterized. Sequences with high scores unique to the SARS-CoV-2 were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates were then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable therapeutic targets for the SARS-CoV-2.
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