The potential of synthetic small interfering RNA-based antiviral drugs for influenza treatment

Пашков, Е. А.; Файзулоев, Е. Б.; Свитич, О. А.; Сергеев, О. В.; Зверев, В. В.

doi:10.36233/0507-4088-2020-65-4-182-190

Cited by 6 publications

(1 citation statement)

References 44 publications

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“…The transcriptomics-based drug works by leveraging RNA as a therapeutic agent [18]. Mainly, siRNA was deployed for deterring other upper respiratory tract viral infections, such as influenza and MERS, and SARS, as proven in the wet laboratory setting [19][20][21][22][23]. The very principle of siRNA deployment is so-called 'preemptive striking', which blocks the viral genes before upregulating the protein expression [24].…”

Section: ■ Introductionmentioning

confidence: 99%

A Computational Design of siRNA in SARS-CoV-2 Spike Glycoprotein Gene and Its Binding Capability toward mRNA

Parikesit

Ansori²,

Kharisma³

2022

Indones. J. Chem.

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COVID-19 pandemic has no immediate ending in sight, and any significant increasing cases were observed worldwide. Currently, there are only two main strategies for developing COVID-19 drugs that predominantly use a proteomics-based approach, which are drug repurposing and herbal medicine strategies. However, a third strategy has existed, called small interfering RNA or siRNA, which is based on the transcriptomics approach. In the case of SARS-CoV-2 infection, it is expected to perform by silencing the viral gene, which brings the surface glycoprotein (S) gene responsible for SARS-CoV-2 viral attachment to the ACE2 receptor on the human host cell. This third approach applies a molecular simulation method comprising data retrieval, multiple sequence alignment, phylogenetic tree depiction, 2D/3D structure prediction, and RNA-RNA molecular docking. The expected results are the prediction of 2D and 3D structures of both siRNA and mRNA silenced S genes along with a complex as the result of a docking method formed by those silenced genes. An Insilco chemical interaction study was performed in testing siRNA and mRNA complex’s stability with the confirmation result of a stable complex which is expected to be formed before mRNA reaches the ribosome for the translation process. Thus, siRNA from the S gene could be considered a candidate for the COVID-19 therapeutic agent.

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Section: ■ Introductionmentioning

confidence: 99%

A Computational Design of siRNA in SARS-CoV-2 Spike Glycoprotein Gene and Its Binding Capability toward mRNA

Parikesit

Ansori²,

Kharisma³

2022

Indones. J. Chem.

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Epidemiology and course of infectious diseases during the covid-19 pandemic. Report 2. Interference engaged between SARS-COV-2 and acute respiratory viral infections

Боева

Belyakov

Simakina

et al. 2022

Russian Journal of Infection and Immunity

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The analytical review, based on the analysis of literature and own materials, outlines the features of the interaction of a new coronavirus infection (COVID-19) and acute respiratory diseases. Particular attention is paid to the combined course of SARS-CoV-2 and the influenza virus, a comparative characteristic of the severity of the clinical picture. An assessment of the epidemic situation against the background of the COVID-19 pandemic in foreign countries and the Russian Federation made it possible to establish the presence of the phenomenon of SARS-CoV-2 interference with other viral respiratory agents, based on the facts of a sharp suppression of the circulation of influenza viruses, respiratory syncytial virus (RSV) and other pathogens of acute respiratory viral infections (ARVI) during the period of active spread of pandemic coronavirus. The results obtained confirm the need to ensure effective surveillance and additional diagnostic capabilities for monitoring SARS, which can significantly affect the decision-making on appropriate preventive measures and clinical management of relevant diseases.

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Investigation of the anti-influenza activity of siRNA complexes against the cellular genes <i>FLT4, Nup98</i>, and <i>Nup205 in vitro</i>

Пашков

Korotysheva

Pak

et al. 2022

Fine Chem. Technol.

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Objectives. Evaluation of changes in the viral activity of influenza A/WSN/33 after complex knockdown of combinations of cellular genes FLT4, Nup98 and Nup205 in human lung cell culture A549. Methods. The work was carried out using the equipment of the Center for Collective Use of the I. Mechnikov Research Institute of Vaccines and Sera, Russia. The authors performed transfection of combinations of small interfering ribonucleic acid (siRNA) complexes that cause simultaneous disruption of the expression of cellular genes FLT4, Nup98, and Nup205. Within three days from the moment of transfection and infection, the supernatant fluid and cell lysate were taken for subsequent viral reproduction intensity determination using the titration method for cytopathic action. The dynamics of changes in the concentration of viral ribonucleic acid (vRNA) was determined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). The nonparametric Mann–Whitney test was used to calculate statistically significant differences between groups.Results. Using all of the combinations of siRNA complexes, cell viability did not decrease below the threshold level of 70%. In cells treated with complex FLT4.2 + Nup98.1 + Nup205 at the multiplicity of infection (MOI) equal to 0.1, a significant decrease in viral reproduction by 1.5 lg was noted on the first day in relation to nonspecific and viral controls. The use of siRNA complexes at MOI 0.01 resulted in a more pronounced antiviral effect. The viral titer in cells treated with siRNA complexes FLT4.2 + Nup98.1 and Nup98.1 + Nup205 decreased by 1.5 lg on the first day. In cells treated with complexes FLT4.2 + Nup205 and FLT4.2 + Nup98.1 + Nup205, it decreased by 1.8 and 2.0 lg on the first day and by 1.8 and 2.5 lg on the second day, respectively, in relation to nonspecific and viral controls. When conducting real-time RT-PCR, a significant decrease in the concentration of vRNA was noted. At MOI 0.1, a 295, 55, and 63-fold decrease in the viral load was observed with the use of siRNA complexes FLT4.2 + Nup98.1, Nup98.1 + Nup205, and FLT4.2 + Nup98.1 + Nup205, respectively. On the second day, a decrease in vRNA was also observed in cells treated with complex A. A 415-fold decrease in vRNA on the third day was noted in cells treated with complex FLT4.2 + Nup205. At MOI 0.01, the concentration of vRNA decreased 9.5 times when using complex B relative to nonspecific and viral control.Conclusions. The study showed a pronounced antiviral effect of siRNA combinations while simultaneously suppressing the activity of cellular genes (FLT4, Nup98, and Nup205), whose expression products are playing important role in the viral reproduction process, and obtained original designs of siRNA complexes. The results obtained are of great importance for the creation of emergence prophylactic and therapeutic drugs, whose action is based on the mechanism of RNA interference.

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The potential of synthetic small interfering RNA-based antiviral drugs for influenza treatment

Cited by 6 publications

References 44 publications

A Computational Design of siRNA in SARS-CoV-2 Spike Glycoprotein Gene and Its Binding Capability toward mRNA

A Computational Design of siRNA in SARS-CoV-2 Spike Glycoprotein Gene and Its Binding Capability toward mRNA

Epidemiology and course of infectious diseases during the covid-19 pandemic. Report 2. Interference engaged between SARS-COV-2 and acute respiratory viral infections

Investigation of the anti-influenza activity of siRNA complexes against the cellular genes <i>FLT4, Nup98</i>, and <i>Nup205 in vitro</i>

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