RAPID: Factors Contributing To Sequence Conservation in the SARS-CoV-2 Genome

RAPID：有助于 SARS-CoV-2 基因组序列保守的因素

• 批准号: 2027611
• 负责人: Andrey Grigoriev
• 金额: $ 18.83万
• 依托单位: Rutgers University Camden
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2027611&HistoricalAwards=false
• 关键词: RAPID; Factors; Contributing; Sequence; Conservation

A novel coronavirus (SARS-CoV-2) emerged in Hubei, China in December 2019 and has since spread rapidly to become a global pandemic. There is a critical need for fundamental research on the biology of this virus and its interactions with the human host to stem the spread of the disease and mitigate its devastating impacts on the global human population. The research supported through this RAPID award will enhance knowledge of how this virus evolves, and it may provide vital clues about its interactions with the human host. Previous research has shown that a critical region of the viral genome is highly conserved, harboring very few mutations compared to the rest of the genome. Exploring the underlying basis for this sequence conservation will reveal new information on factors that could influence the spread, diagnostics and treatment of SARS-CoV-2. The project also offers training opportunities for graduate and undergraduate students, and will support development of a web-based tool for the community to study viral genome evolution. The PI has identified a region of the SARS-Cov-2 genome, which includes the RNA-dependent RNA polymerase (RdRp), which has extremely high conservation at the nucleotide level. This finding suggests that selection is acting to maintain sequence motifs in this region, possibly pointing to structural constraints on the RdRp RNA or RNA-mediated interactions between the virus and host. The project will explore a range of hypotheses about selection factors, including noncoding RNAs, RNA secondary structure and RNA binding sites for host proteins, among others, that could account for the sequence conservation. The project will also attempt a study relating these factors to human susceptibility to SARS-CoV-2, if access is gained to patient data on genome variation and corresponding infection severity. This RAPID award is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

一种新型冠状病毒(SARS-CoV-2)于2019年12月在湖北中国出现，此后迅速传播，成为全球大流行。迫切需要对该病毒的生物学及其与人类宿主的相互作用进行基础研究，以阻止该疾病的传播并减轻其对全球人口的破坏性影响。通过这一快速奖项支持的研究将加强对这种病毒如何进化的了解，并可能提供有关其与人类宿主相互作用的重要线索。先前的研究表明，病毒基因组的一个关键区域是高度保守的，与基因组的其余部分相比，突变很少。探索这种序列保守的潜在基础将揭示有关可能影响SARS-CoV-2传播、诊断和治疗的因素的新信息。该项目还为研究生和本科生提供培训机会，并将支持开发一个基于网络的工具，供社区研究病毒基因组进化。PI已经确定了SARS-CoV-2基因组的一个区域，其中包括RNA依赖的RNA聚合酶(RdRp)，它在核苷酸水平上具有极高的保守性。这一发现表明，选择在该区域维持序列基序，可能指向对RdRp RNA或RNA介导的病毒与宿主之间相互作用的结构限制。该项目将探索一系列关于选择因素的假设，包括非编码RNA、RNA二级结构和宿主蛋白的RNA结合位点等，这些假设可以解释序列保守。如果获得有关基因组变异和相应感染严重程度的患者数据，该项目还将尝试进行一项研究，将这些因素与人类对SARS-CoV-2的易感性联系起来。这一快速奖项由分子和细胞生物科学部的遗传机制计划资助。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

SARSNTdb database: Factors affecting SARS-CoV-2 sequence conservation

• DOI: 10.3389/fviro.2022.1028335
• 发表时间: 2022-12-01
• 期刊: FRONTIERS IN VIROLOGY
• 作者: Orgera，John;Kelley，James J.;Grigoriev，Andrey
• 通讯作者: Grigoriev，Andrey