Crippled Coronavirus: 5’-PolyU targeted Oligo prevents development of infectious Virions
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Abstract
Current RNA viral pandemic of COVID-19 has been worsened by rapidly spreading viral variants. To inhibit mutation-based development of new escape variants, elements that are indispensable for the virus may be targeted. The 5’-polyU tract of the antigenome offers one such target. Host cells do not harbor 5’-polyU tracts on any of their transcripts, making the tract an attractive virus-specific target. We hypothesize that inhibiting the 5’-polyU by complementary oligonucleotide can limit the use of the tract as template for virus to generate 3’ polyA tails of RNA viruses. Here, we used a frameshift-inducing DNA oligonucleotide with 3’ polyAs to target the 5’-polyU tract of mouse coronavirus (MHV-A59). Results from assays for double stranded RNA (dsRNA) synthesis, infectivity of released virions, and syncytium formation indicate that the oligonucleotide treatment prevented generation of infectious virions. Our results show a unique mode of action of the designed 3’-polyA oligonucleotide against mouse coronavirus which leaves host cells unaffected. This strategy can be adopted for the development of novel classes of oligonucleotide-based drugs that inhibit the production of infectious RNA viruses, including the coronaviruses. Since the 5’-polyU tract is conserved and is essential for variants of coronaviruses, this strategy can potentially address coronavirus variant emergence as well.
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SciScore for 10.1101/2022.03.04.483076: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources The washed cells were incubated in a humified 4C chamber overnight with the anti-dsRNA antibody (1:250) in PBST with 1% BSA. anti-dsRNAsuggested: (Millipore Cat# MABE1134, RRID:AB_2819101)The cells were washed three times in PBS, 5 min each wash and then Incubated cells with the anti-mouse TRITC conjugated secondary antibody (1:1000) in 1% BSA for 1 h at room temperature in the dark. anti-mouse TRITCsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources MHV strain A59-eGFP, which express the Enhanced Green … SciScore for 10.1101/2022.03.04.483076: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources The washed cells were incubated in a humified 4C chamber overnight with the anti-dsRNA antibody (1:250) in PBST with 1% BSA. anti-dsRNAsuggested: (Millipore Cat# MABE1134, RRID:AB_2819101)The cells were washed three times in PBS, 5 min each wash and then Incubated cells with the anti-mouse TRITC conjugated secondary antibody (1:1000) in 1% BSA for 1 h at room temperature in the dark. anti-mouse TRITCsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources MHV strain A59-eGFP, which express the Enhanced Green Fluorescent Protein (eGFP) inserted in place of the Ns4 gene, was obtained through BEI Resources, NIAID, NIH, catalog number: NR-53716. A59-eGFPsuggested: 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.
Results from scite Reference Check: We found no unreliable references.
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