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利用计算方法发现基于RNA干扰疗法治疗新冠肺炎的潜在候选药物。

DisCoVering potential candidates of RNAi-based therapy for COVID-19 using computational methods.

作者信息

Rohani Narjes, Ahmadi Moughari Fatemeh, Eslahchi Changiz

机构信息

Department of Computer and Data Sciences, Faculty of Mathematical Sciences, Shahid Beheshti University, Tehran, Iran.

School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.

出版信息

PeerJ. 2021 Feb 26;9:e10505. doi: 10.7717/peerj.10505. eCollection 2021.

Abstract

The ongoing pandemic of a novel coronavirus (SARS-CoV-2) leads to international concern; thus, emergency interventions need to be taken. Due to the time-consuming experimental methods for proposing useful treatments, computational approaches facilitate investigating thousands of alternatives simultaneously and narrow down the cases for experimental validation. Herein, we conducted four independent analyses for RNA interference (RNAi)-based therapy with computational and bioinformatic methods. The aim is to target the evolutionarily conserved regions in the SARS-CoV-2 genome in order to down-regulate or silence its RNA. miRNAs are denoted to play an important role in the resistance of some species to viral infections. A comprehensive analysis of the miRNAs available in the body of humans, as well as the miRNAs in bats and many other species, were done to find efficient candidates with low side effects in the human body. Moreover, the evolutionarily conserved regions in the SARS-CoV-2 genome were considered for designing novel significant siRNA that are target-specific. A small set of miRNAs and five siRNAs were suggested as the possible efficient candidates with a high affinity to the SARS-CoV-2 genome and low side effects. The suggested candidates are promising therapeutics for the experimental evaluations and may speed up the procedure of treatment design. Materials and implementations are available at: https://github.com/nrohani/SARS-CoV-2.

摘要

新型冠状病毒(SARS-CoV-2)的持续流行引起了国际关注;因此,需要采取紧急干预措施。由于提出有效治疗方法的实验方法耗时,计算方法有助于同时研究数千种替代方案,并缩小实验验证的范围。在此,我们采用计算和生物信息学方法对基于RNA干扰(RNAi)的疗法进行了四项独立分析。目的是靶向SARS-CoV-2基因组中进化保守区域,以下调或沉默其RNA。微小RNA(miRNA)在某些物种对病毒感染的抗性中起着重要作用。对人体以及蝙蝠和许多其他物种体内的miRNA进行了全面分析,以寻找在人体中副作用小的有效候选物。此外,在设计具有靶向特异性的新型有效小干扰RNA(siRNA)时考虑了SARS-CoV-2基因组中的进化保守区域。一小部分miRNA和五种siRNA被认为是对SARS-CoV-2基因组具有高亲和力且副作用小的可能有效候选物。所建议的候选物是用于实验评估的有前景的治疗方法,可能会加快治疗设计的进程。材料和实施方法可在以下网址获取:https://github.com/nrohani/SARS-CoV-2

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/578c/7919535/df70e6b94d2d/peerj-09-10505-g001.jpg

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