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靶向 SARS-CoV-2(印度分离株)基因组的 miRNA:一项计算机研究。

Targeting SARS CoV2 (Indian isolate) genome with miRNA: An in silico study.

机构信息

Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, India.

Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.

出版信息

IUBMB Life. 2020 Nov;72(11):2454-2468. doi: 10.1002/iub.2373. Epub 2020 Sep 10.

Abstract

The newly identified SARS CoV2 has become a global pandemic since December 2019. Various researchers are trying to design a vaccine candidate against the virus. On the other hand, another group is focussing on repurposing approved or clinically tested drugs for treatment. However, there is always a search for alternative therapies. Thus, we propose an alternative approach apart from chemotherapy that is the usage of miRNA as novel antisense therapy to cure SARS CoV2 infected patients. To address the objective, miRNAs have been designed by targeting the genome of SARS CoV2 (Indian isolate). First, the open reading frames in the viral genome have been identified, and the proteins encoded by those open reading frames have been predicted. Using computational biology, several miRNAs have been designed and their probability to bind to a viral gene has been predicted. In addition, miRNA target mining in the host cell has been done to rule out the possibility of non-specific binding of the miRNAs. The miRNAs having the highest chances to bind to the viral genome have been converted into pre-miRNAs, and their interaction with dicer endoribonuclease has been studied by molecular docking. Results revealed that the pre-miRNAs interact with the RNAse III 2 domain of dicer. Thus, it is predicted that the pre-miRNAs after delivery to the infected host cell will be processed by dicer to generate mature miRNAs that will target the SARS CoV2 viral genome. Therefore, miRNA therapy can be an alternative approach for the treatment of SARS CoV2 infection.

摘要

自 2019 年 12 月以来,新发现的严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)已成为全球大流行。各种研究人员都在试图设计针对该病毒的候选疫苗。另一方面,另一组研究人员则专注于重新利用已批准或经过临床测试的药物进行治疗。然而,人们总是在寻找替代疗法。因此,我们提出了一种除化疗之外的替代方法,即使用 miRNA 作为治疗 SARS-CoV-2 感染患者的新型反义疗法。为了实现这一目标,我们通过针对 SARS-CoV-2(印度分离株)的基因组来设计 miRNA。首先,确定了病毒基因组中的开放阅读框,并预测了这些开放阅读框编码的蛋白质。通过计算生物学,我们设计了几种 miRNA,并预测了它们与病毒基因结合的可能性。此外,还对宿主细胞中的 miRNA 靶标进行了挖掘,以排除 miRNA 非特异性结合的可能性。选择与病毒基因组结合可能性最高的 miRNA 转化为 pre-miRNA,并通过分子对接研究它们与 dicer 内切核糖核酸酶的相互作用。结果表明,pre-miRNA 与 dicer 的 RNAse III 2 结构域相互作用。因此,可以预测,递送到感染宿主细胞的 pre-miRNA 将被 dicer 加工生成靶向 SARS-CoV-2 病毒基因组的成熟 miRNA。因此,miRNA 疗法可能是治疗 SARS-CoV-2 感染的一种替代方法。

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