新型冠状病毒基因组G-四链体结构的初步研究

Preliminary Study on the Structure of G-Quadruplexes in the Genome of SARS-CoV-2

21世纪以来,冠状病毒频频引起危害人类健康的重要传染病,其中包括2003年严重急性呼吸综合征冠状病毒(SARS-CoV)、2012年中东呼吸综合征冠状病毒(MERS-CoV)和新型冠状病毒(SARS-CoV-2),目前对这些病毒引发的疾病并无特效的治疗药物。G-四链体(G-quadruplex,G4)是在DNA或RNA的鸟嘌呤富集区形成的非典型二级结构,可存在于人类和病毒基因组中,G-四链体的不同位置对病毒复制和感染等过程发挥重要调控作用。本研究针对七种与人类疾病相关的冠状病毒以及与SARS-CoV-2同源性较高的三种蝙蝠相关病毒,通过全基因组序列分析潜在四链体形成序列(Potential quadruplex-forming sequences,PQS),结果发现,十种病毒中均存在一定数量的PQS基序,同时对SARS-CoV-2 G-四链体存在位置及形成潜力进行评估,并分析了不同变异株间G-四链体基序的保守性。本研究对SARS-CoV-2基因组中G-四链体进行初步预测与探讨,旨在为COVID-19治疗提供一种新的药物靶点,使其更好地应用于临床研究。

Since the dawn of the 21 st century,coronaviruses have caused important infectious diseases harmful to human health,including severe acute respiratory syndrome coronavirus(SARS-CoV)in 2003,Middle East respiratory syndrome coronavirus in 2012,and SARS-CoV-2 in 2019(which is ongoing).A specific treatment for the diseases caused by these coronaviruses is lacking.G-quadruplexes are atypical secondary structures formed in guanine-rich regions of DNA or RNA that can exist in the genomes of humans and viruses.Different positions of G-quadruplexes have important roles in regulation of the replication and infection of viruses.We analyzed the potential quadruplex formation sequence(PQS)of seven coronaviruses related to human diseases and three bat-related viruses with high homology to SARS-CoV-2.We noted a certain number of PQS motifs in all 10 viruses.Simultaneously,the existence,location and formation potential of G-quadruplexes in SARS-CoV-2 were evaluated.Conservation of G-quadruplex motifs among different mutants was analyzed.We made a preliminary prediction and discussed G-quadruplexes in the genome of SARS-CoV-2.In this way,we provided a new drug target for treatment of COVID-19.