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/s12539-015-0266-9

Cited by 40 publications

(29 citation statements)

References 40 publications

(42 reference statements)

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“…GO-based gene enrichment analysis demonstrated that many involved biological processes were closely related to the immune response ( Fig 3A ), including myeloid cell activation and neutrophil activation ( Fig 3C and 3E ). Interestingly, the miRNAs-related gene pathways were overexpressed as a response to SARS-CoV-2 infection, and they are known to play an important role against viral infection [ 19 ]. Activation of miRNAs as a defense mechanism during lung infection could be related to their important roles in physiological and pathological processes in the lung [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The transcriptomic profiling of SARS-CoV-2 compared to SARS, MERS, EBOV, and H1N1

Alsamman

Zayed

2020

PLoS ONE

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The SARS-CoV-2 (COVID-19) pandemic is a global crisis that threatens our way of life. As of November 18, 2020, SARS-CoV-2 has claimed more than 1,342,709 lives, with a global mortality rate of ~2.4% and a recovery rate of ~69.6%. Understanding the interaction of cellular targets with the SARS-CoV-2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of SARS-CoV-2 compared to other respiratory viruses (EBOV, H1N1, MERS-CoV, and SARS-CoV), to determine a unique anti-SARS-CoV-2 gene signature. We identified for the first time that molecular pathways for heparin-binding, RAGE, miRNA, and PLA2 inhibitors were associated with SARS-CoV-2 infection. The NRCAM and SAA2 genes, which are involved in severe inflammatory responses, and the FGF1 and FOXO1 genes, which are associated with immune regulation, were found to be associated with the cellular gene response to SARS-CoV-2 infection. Moreover, several cytokines, most significantly IL-8 and IL-6, demonstrated key associations with SARS-CoV-2 infection. Interestingly, the only response gene that was shared among the five viral infections was SERPINB1. The protein-protein interaction (PPI) analysis shed light on genes with high interaction activity that SARS-CoV-2 shares with other viral infections. The findings showed that the genetic pathways associated with rheumatoid arthritis, the 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 SARS-CoV-2 and EBOV were more similar than to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

The transcriptomic profiling of SARS-CoV-2 compared to SARS, MERS, EBOV, and H1N1

Alsamman

Zayed

2020

PLoS ONE

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“…In the context of MERS-CoV the ORF1ab region encoding the replicase polyproteins plays a vital role in viral infection and therefore represents a suitable target for disease control. Four miRNA and five siRNA molecules were rationally designed by computational methods for silencing of nine different MERS-CoV strains for exploration of the treatment of MERS-CoV at the genomic level [124]. In attempts to optimize delivery of MERS-CoV siRNAs, transfection, electroporation and viral gene transfers have been applied.…”

Section: Gene Silencingmentioning

confidence: 99%

Coronavirus Pandemic—Therapy and Vaccines

Lundström¹

2020

Biomedicines

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The current coronavirus COVID-19 pandemic, which originated in Wuhan, China, has raised significant social, psychological and economic concerns in addition to direct medical issues. The rapid spread of severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 to almost every country on the globe and the failure to contain the infections have contributed to fear and panic worldwide. The lack of available and efficient antiviral drugs or vaccines has further worsened the situation. For these reasons, it cannot be overstated that an accelerated effort for the development of novel drugs and vaccines is needed. In this context, novel approaches in both gene therapy and vaccine development are essential. Previous experience from SARS-and MERS-coronavirus vaccine and drug development projects have targeted glycoprotein epitopes, monoclonal antibodies, angiotensin receptor blockers and gene silencing technologies, which may be useful for COVID-19 too. Moreover, existing antivirals used for other types of viral infections have been considered as urgent action is necessary. This review aims at providing a background of coronavirus genetics and biology, examples of therapeutic and vaccine strategies taken and potential innovative novel approaches in progress.

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“…The design of siRNAs has also been based on analysis of nucleotide frequency at multiple locations in siRNAs [ 32 ] and the selection of effective siRNAs directed against conserved regions of HIV, hepatitis C (HCV), influenza virus and SARS-CoV [ 33 ]. The Viral siRNA Predictor was developed based on published data using features such as nucleotide frequency, thermodynamic factors and nucleotide location for prediction of siRNA targeting of pathogenic viruses [ 34 ]. However, the RNA structure might impose restrictions for RNA therapy based on properties of the HCV genome from primary sequence to tertiary structure [ 35 ].…”

Section: Rnai and Bioinformaticsmentioning

confidence: 99%

Viral Vectors Applied for RNAi-Based Antiviral Therapy

Lundström¹

2020

Viruses

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RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-viral delivery of RNAi molecules. On the other hand, utilization of viral vectors and particularly self-replicating RNA virus vectors can be considered as an attractive alternative. In this review, examples of antiviral therapy applying RNAi-based approaches in various animal models will be described. Due to the current coronavirus pandemic, a special emphasis will be dedicated to targeting Coronavirus Disease-19 (COVID-19).

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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 40 publications

References 40 publications

The transcriptomic profiling of SARS-CoV-2 compared to SARS, MERS, EBOV, and H1N1

The transcriptomic profiling of SARS-CoV-2 compared to SARS, MERS, EBOV, and H1N1

Coronavirus Pandemic—Therapy and Vaccines

Viral Vectors Applied for RNAi-Based Antiviral Therapy

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