Center for dynamic RNA epitranscriptomes - Covid 19 Supplement Version 2

摘要 SARS-CoV-2病毒RNA修饰的定量测序及宿主鉴定 病毒RNA复制的关键修饰酶 一种新的冠状病毒病(被称为新冠肺炎)席卷了200个国家，并被宣布为 大流行。病原体被命名为严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)。目前还没有针对SARS-CoV-2的有效疫苗。FDA已经 批准两种抗疟疾药物氯喹和羟基氯喹紧急用于 新冠肺炎的治疗。此外，用于治疗埃博拉病毒的核苷酸类似物瑞德韦尔 病毒病，目前正在进行临床试验和临床使用，用于新冠肺炎治疗。理解 SARS-CoV-2的特性和揭示其感染所必需的细胞成分至关重要 在不久的将来开发有效的治疗方法和疫苗。 SARS-CoV-2是一种RNA病毒。它的病毒RNA已经被证明是经过化学修饰的。 我们和其他人之前的研究揭示了病毒RNA修饰在病毒中的关键作用 复制和免疫逃避。我们的最新数据表明，一种RNA M5C 甲基转移酶NSUN2在人类冠状病毒在宿主细胞内复制过程中起着至关重要的作用。在……里面 这项行政补充申请，我们建议应用定量测序方法 由我们的CEGS开发用于定位N6-甲基腺苷(M6A)、5-甲基胞嘧啶(M5C)、 假尿苷(Ψ)、2‘-O-甲基化(Nm)、N7-甲基鸟苷(M7G)和N1-甲基腺苷 (M1a)在SARS-CoV-2RNA中。我们还将分配修饰酶并测试其对 利用已建立的SARS-CoV-2感染模型进行病毒感染。我们将专门研究 NSUN2及其对病毒RNA M5C甲基化的影响，并测试已知的抑制病毒的抑制剂 感染。我们还将研究m6A和相关修饰在保护病毒方面的潜在作用。 来自宿主先天免疫反应的RNA。

Abstract Quantitative sequencing of SARS-CoV-2 viral RNA modifications and identification of host modification enzymes critical to viral RNA replication A new coronavirus disease (known as COVID-19) has swept 200 countries and was declared a pandemic. The causative agent is named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is no effective vaccine currently available for SARS-CoV-2. FDA has approved two anti-malaria drugs, chloroquine and hydroxychloroquine, for emergency use for treatment of COVID-19. In addition, remdesivir, a nucleotide analog used for treatment of Ebola virus disease, is now in clinical trials and clinical use for COVID-19 treatment. Understanding properties of SARS-CoV-2 and revealing cellular components essential to its infection are critical to development of effective therapies and vaccines in the near future. SARS-CoV-2 is an RNA virus. Its viral RNAs have been shown to be chemically modified. Previous studies from us and others have revealed crucial roles of viral RNA modifications in viral replication and immune evasion. Our most recent data indicate that an RNA m5C methyltransferase NSUN2 plays a vital role in human coronavirus replication inside host cells. In this administrative supplement application we propose to apply quantitative sequencing methods developed by our CEGS to map N6-methyladenosine (m6A), 5-methylcytosine (m5C), pseudouridine (Ψ), 2’-O-methylation (Nm), N7-methylguanosine (m7G) and N1-methyladenosine (m1A) in SARS-CoV-2 RNA. We will also assign modification enzymes and test their effects on viral infection using established infection models of SARS-CoV-2. We will specifically examined NSUN2 and its effect on viral RNA m5C methylation, and test known inhibitors for inhibition of viral infection. We will also examine potential roles of m6A and related modifications in protecting viral RNA from host innate immune responses.