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通过计算方法设计用于中东呼吸综合征冠状病毒(MERS-CoV)基因沉默的潜在RNA干扰(miRNA和siRNA)分子。

Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method.

作者信息

Nur Suza Mohammad, Hasan Md Anayet, Amin Mohammad Al, Hossain Mehjabeen, Sharmin Tahmina

机构信息

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

出版信息

Interdiscip Sci. 2014 Nov 6. doi: 10.1007/s12539-014-0233-x.

DOI:10.1007/s12539-014-0233-x
PMID:25519155
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 ORF 1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF 1ab replicase polyprotein may be used as 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 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,其表现为病毒感染,症状包括发热、咳嗽、呼吸急促、肾衰竭和严重的急性肺炎,这些症状往往会导致致命的后果。已证明MERS-CoV可在密切接触的人群之间传播。也观察到了从感染患者传播给医护人员的情况,并且以目前的技术无法挽回。对MERS-CoV的基因研究表明,开放阅读框1ab(ORF 1ab)编码复制酶多聚蛋白,在病毒感染中起首要作用。因此,ORF 1ab复制酶多聚蛋白可作为疾病控制的合适靶点。病毒活性可以通过RNA干扰(RNAi)技术来控制,RNAi技术是一种以序列特异性方式进行转录后基因沉默的主要方法。然而,不同病毒分离株存在基因不一致性;设计能够特异性沉默各自靶基因而非同时沉默任何其他病毒基因的潜在RNAi(微小RNA和小干扰RNA)分子是一项巨大的挑战。在当前的研究中,利用计算方法合理设计并证实了四种有效的微小RNA和五种小干扰RNA分子,用于沉默九种不同株系的MERS-CoV,这可能会降低病毒的活性。利用计算方法预测针对不同株系MERS-CoV的ORF1ab基因的小干扰RNA和微小RNA分子为有效的候选分子。因此,这种方法可能为在基因组水平上化学合成用于治疗MERS-CoV的抗病毒RNA分子提供思路。

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