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中东呼吸综合征冠状病毒(MERS-CoV)基因沉默的潜在 RNAi(miRNA 和 siRNA)分子的计算方法设计。

Design of Potential RNAi (miRNA and siRNA) Molecules for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Gene Silencing by Computational Method.

机构信息

Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong, 4331, Bangladesh.

Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Bangladesh.

出版信息

Interdiscip Sci. 2015 Sep;7(3):257-65. doi: 10.1007/s12539-015-0266-9. Epub 2015 Jul 30.

DOI:10.1007/s12539-015-0266-9
PMID:26223545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7090891/
Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that manifests itself in viral infection with fever, cough, shortness of breath, renal failure and severe acute pneumonia, which often result in a fatal outcome. MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed and is irredeemable with present technology. Genetic studies on MERS-CoV have shown that ORF1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF1ab replicase polyprotein may be used as a suitable target for disease control. Viral activity can be controlled by RNA interference (RNAi) technology, a leading method for post transcriptional gene silencing in a sequence-specific manner. However, there is a genetic inconsistency in different viral isolates; it is a great challenge to design potential RNAi (miRNA and siRNA) molecules which can silence the respective target genes rather than any other viral gene simultaneously. In the current study, four effective miRNA and five siRNA molecules for silencing of nine different strains of MERS-CoV were rationally designed and corroborated using computational methods, which might lead to knockdown the activity of virus. siRNA and miRNA molecules were predicted against ORF1ab gene of different strains of MERS-CoV as effective candidate using computational methods. Thus, this method may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of MERS-CoV, at genomic level.

摘要

中东呼吸综合征冠状病毒(MERS-CoV)是一种病毒,表现为病毒感染,伴有发热、咳嗽、呼吸急促、肾衰竭和严重急性肺炎,这些症状常常导致致命的结果。已经证明,MERS-CoV 在密切接触的人群之间传播。也观察到从感染患者到医护人员的传播,目前的技术无法挽回。对 MERS-CoV 的遗传研究表明,ORF1ab 编码复制酶多蛋白,在病毒感染中起主要作用。因此,ORF1ab 复制酶多蛋白可能被用作疾病控制的合适靶标。病毒活性可以通过 RNA 干扰(RNAi)技术来控制,这是一种在序列特异性的方式下进行转录后基因沉默的主要方法。然而,不同病毒分离株之间存在遗传不一致性;设计能够沉默各自靶基因而不是同时沉默任何其他病毒基因的潜在 RNAi(miRNA 和 siRNA)分子是一个巨大的挑战。在当前的研究中,使用计算方法合理设计了针对 MERS-CoV 的 9 种不同株系的 4 种有效的 miRNA 和 5 种 siRNA 分子,并进行了验证,这可能导致病毒活性的降低。使用计算方法针对不同株系的 MERS-CoV 的 ORF1ab 基因预测了 siRNA 和 miRNA 分子作为有效的候选物。因此,该方法可能为治疗 MERS-CoV 的抗病毒 RNA 分子的化学合成提供一个在基因组水平上的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/3178b76fbb2a/12539_2015_266_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/f1a870beeada/12539_2015_266_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/0eb0729c857f/12539_2015_266_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/3178b76fbb2a/12539_2015_266_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/f1a870beeada/12539_2015_266_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/0eb0729c857f/12539_2015_266_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/7090891/3178b76fbb2a/12539_2015_266_Fig3_HTML.jpg

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