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

Nur, Suza Mohammad; Hasan, Md. Anayet; Amin, Mohammad Al; Hossain, M. Amzad; Sharmin, Tahmina

doi:10.1007/s12539-014-0208-y

Cited by 18 publications

(32 citation statements)

References 37 publications

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“…GO-based gene enrichment analysis demonstrated that many biological processes are closely related to the immune response (Figure 2A), including myeloid cell activation and neutrophil activation (Figure 4C and 4E). Interestingly, miRNAs-related gene pathway was overexpressed as a response to COVID-19 infection, which is known to play an important role against viral infection (Nur et al 2015). Activation of miRNAs as a defense mechanism during lung infection could be related to its important role in physiological and pathological processes in the lung (Tomankova et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

Alsamman

Zayed

2020

Preprint

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COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of~7% and recovery rate of~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19.

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Section: Discussionmentioning

confidence: 99%

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

Alsamman

Zayed

2020

Preprint

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“…So far, a number of experimental rules on siRNA duplex features have been frequently reported. These include the asymmetry rules for siRNA duplex ends, high A/U content at the 5'-end of the antisense strand, high G/C content at the 5'-end of sense strand, 30-50% GC content, thermodynamic properties in term of the secondary structures, accessibilities of siRNA and target mRNA of gene(s) of interest (Nur et al, 2014). Therefore, the plant short small RNA interfering tool (pssRNAit web tool), which provides a functional and an off-target minimized siRNA design, was used to in-silico identifying efficient siRNAs candidates in the target mRNAs (Http://plantgrn.noble.org/pssRNAit/).…”

Section: Determination Of Multiple Sirna Candidatesmentioning

confidence: 99%

“…The DNA/RNA GC content calculator (http://www.endmemo.com/Tools/Biology) was used to calculate the GC content of the predicted siRNA. For checking any off-target sequence resemblance in other non-targeted organism's genome, the BLAST tool (http://www.ncbi.nlm.nih.gov/blast) was used against the whole GenBank database by applying expected thresholds value 10 and BLOSUM 62 matrix as parameter (Nur et al, 2014).…”

Section: Gc Calculation and Off-target Alignmentmentioning

confidence: 99%

“…All the siRNA holds GC content within 36-48% were determined by GC content calculator. Lower GC content leads to stronger inhibitory effects and 30-57% of GC content is considered sufficient for the execution of RNAi's action (Nur et al, 2014;Bret et al, 2005;Liu et al, 2013). Consequently, after the analysis of all siRNA candidates, six potential siRNAs, which were consecutively arranged in the target repeats, were considered as the efficient candidates for effective triggering γ-gliadin target mRNAs.…”

Section: Identification Of Potent Sirnasmentioning

confidence: 99%

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Design , Cloning and in Silico Analysis of Efficient Sirnainducing Cassette for Silencing Wheat γ-Gliadins

Kohnehrouz¹,

Nayeri²

2016

JJBS

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Gluten is an important protein source for human beings and a wide diversity of foods has been developed to take advantage of this protein in wheat flour. However, some individuals, suffering from Celiac Disease (CD), cannot tolerate proline and glutamine-rich gluten peptides including γ-gliadins. A life-long gluten free diet is the only known effective treatment for such patients. However, the sensitivity intension in CD patients can be controlled by RNA interference (RNAi) technology. The main aim of the present study is to develop an efficient and specific siRNA-inducing cassette, as a first and critical step for an effective targeting of mRNAs of wheat γ-gliadins. To achieve this aim, we have followed the strategy based on 200 bp in sense and antisense orientation with the ~160bp sequence of none potent siRNA-containing region from γgliadin gene as a spacer in between. The endosperm-specific γ-gliadin promoter was sub-cloned into upstream the cassette. The nucleotide alignment results validated the sequence data of γ-gliadin promoter and the direct inserts with high homology identities of 99% and 99.97%, respectively. Here, six potential and consecutively arranged-siRNA sites were predicted using computational approaches. All of these sites covered the inverted repeats region with high efficacy and performance values for triggering RNAi. Abbreviations :CD Celiac Disease, CTAB Cetyl Triethyl Ammonium Bromide, dNTPs deoxy nucleoside5´-triphosphates, dsRNA double strand RNA, hpRNA hairpin RNA, HMW High Molecular Weight, IPTG Isopropyl β-D-1-thiogalactopyranoside, kD kilo Dalton, LB Luria Bertani, LMW Low molecular weight, MFE Minimum Free Energy, mRNA messenger RNA, NCBI National Center for Biotechnological Information, PCR Polymerase Chain Reaction ,pssRNAit plant short small RNA interfering tool, PTGS Post Transcriptional Gene Silencing, RISC RNA-Induced Silencing Complex, RNAi RNA interference, siRNA small interfering RNA, UPE Unpaired Energy, `X-gal 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside,

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“…Based on this property of miRNA, attempts have been made to regulate the expression of viral genes using natural miRNAs or by creating synthetic small interfering RNAs (siRNAs) [4][5][6]. In some cases, this approach gave a positive result in vitro but was not applicable in vivo for several reasons, including the lack of evidence that miRNA and siRNA do not have side effects in humans or experimental animals [7][8][9][10].…”

mentioning

confidence: 99%

The miRNA Complexes Against Coronaviruses COVID-19, SARS-CoV, And MERS-CoV

Rakhmetullina

Иващенко

Akimniyazova

et al. 2020

Preprint

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Background: In the past twenty years humankind has effected from infection caused by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and COVID-19 coronaviruses, which have caused significant harm to human health and resulted in high mortality. The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses COVID-19, SARS-CoV, and MERS-CoV has been shown. Methods: The MirTarget program determines the following characteristics of interaction between miRNAs and messenger RNAs (mRNAs): the start of the miRNA binding site on the mRNA; the locations of the miRNA binding sites in the 3'-untranslated region (3'UTR), 5'-untranslated region (5'UTR), or coding sequence (CDS); the interaction free energy (∆G, kJ/mole); and nucleotide interaction schemes between miRNAs and mRNAs. Results: Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of COVID-19, SARS-CoV, and MERS-CoV genomes. For complexes of seven completely complementary miRNA of COVID-19 (cc-miRc), seven completely complementary miRNA of SARS-CoV (cc-miRs), and eight completely complementary miRNA of MERS-CoV (cc-miRm), the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. Conclusion: The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

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

Cited by 18 publications

References 37 publications

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

Design , Cloning and in Silico Analysis of Efficient Sirnainducing Cassette for Silencing Wheat γ-Gliadins

The miRNA Complexes Against Coronaviruses COVID-19, SARS-CoV, And MERS-CoV

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