Potential Opportunity of Antisense Therapy of COVID-19 on an in Vitro Model
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Abstract
Data on potential effectiveness and prospects of treatment of new coronavirus infection of COVID-19 caused by virus SARS-CoV-2 with the help of antisense oligonucleotides acting against RNA of virus on an in vitro model are given. The ability of antisense oligonucleotides to suppress viral replication in diseases caused by coronaviruses using the example of SARS and MERS is shown. The identity of the initial regulatory section of RNA of various coronaviruses was found within 50 - 100 nucleotides from the 5’-end, which allows using antisense suppression of this RNA fragment. A new RNA fragment of the virus present in all samples of coronovirus SARS-CoV-2 has been identified, the suppression of which with the help of an antisense oligonucleotide can be effective in the treatment of COVID-19. The study of the synthesized antisense oligonucleotide 5’ - AGCCGAGTGACAGCC ACACAG, complementary to the selected virus RNA sequence, was carried out. The low toxicity of the preparations of this group in the cell culture study and the ability to reduce viral load at high doses according to real time-PCR data are shown. The cytopathogenic dose exceeds 2 mg / ml. At a dosage of 1 mg / ml, viral replication is reduced by 5-13 times. Conclusions are made about the prospects of this direction and the feasibility of using the inhalation way of drug administration into the body.
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SciScore for 10.1101/2020.11.02.363598: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The study of the antiviral activity of the antisense oligonucleotide substance in the Vero E6 cell culture was carried out with a choice of concentrations based on the results of the cytotoxicity study. Vero E6suggested: RRID:CVCL_XD71)The assessment of antiviral activity of the drug in addition to cytopathic action was also taken into account by reducing the infectious titer of the virus in the culture of Vero cells E6 according to … SciScore for 10.1101/2020.11.02.363598: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The study of the antiviral activity of the antisense oligonucleotide substance in the Vero E6 cell culture was carried out with a choice of concentrations based on the results of the cytotoxicity study. Vero E6suggested: RRID:CVCL_XD71)The assessment of antiviral activity of the drug in addition to cytopathic action was also taken into account by reducing the infectious titer of the virus in the culture of Vero cells E6 according to PCR RNA SARS-CoV-2, determined by the threshold of the number of reaction cycles (cycle treshold, Ct) in various dilutions of the study drug. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources BLAST analysis on the GenBank (NCBI) showed presence of this sequence at genomes of all sequenced samples SARS-CoV-2. BLASTsuggested: (BLASTX, RRID:SCR_001653)After incubation for 3 hours at 37 °C, the results were taken into account on the BIORAD automatic reader at a wavelength of 490 nm. BIORADsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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