ROS/RNS Balancing, Aerobic Fermentation Regulation and Cell Cycle Control – a Complex Early Trait (‘CoV-MAC-TED’) for Combating SARS-CoV-2-Induced Cell Reprogramming

  1. José Hélio Costa
  2. Gunasekaran Mohanapriya
  3. Revuru Bharadwaj
  4. Carlos Noceda
  5. Karine Leitão Lima Thiers
  6. Shahid Aziz
  7. Shivani Srivastava
  8. Manuela Oliveira
  9. Kapuganti Jagadis Gupta
  10. Aprajita Kumari
  11. Debabrata Sircar
  12. Sarma Rajeev Kumar
  13. Arvind Achra
  14. Ramalingam Sathishkumar
  15. Alok Adholeya
  16. Birgit Arnholdt-Schmitt

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Abstract

In a perspective entitled ‘From plant survival under severe stress to anti-viral human defense’ we raised and justified the hypothesis that transcript level profiles of justified target genes established from in vitro somatic embryogenesis (SE) induction in plants as a reference compared to virus-induced profiles can identify differential virus signatures that link to harmful reprogramming. A standard profile of selected genes named ‘ReprogVirus’ was proposed for in vitro -scanning of early virus-induced reprogramming in critical primary infected cells/tissues as target trait. For data collection, the ‘ReprogVirus platform’ was initiated. This initiative aims to identify in a common effort across scientific boundaries critical virus footprints from diverse virus origins and variants as a basis for anti-viral strategy design. This approach is open for validation and extension. In the present study, we initiated validation by experimental transcriptome data available in public domain combined with advancing plant wet lab research. We compared plant-adapted transcriptomes according to ‘RegroVirus’ complemented by alternative oxidase (AOX) genes during de novo programming under SE-inducing conditions with in vitro corona virus-induced transcriptome profiles. This approach enabled identifying a ma jor c omplex t rait for e arly de novo programming during SARS-CoV-2 infection, called ‘CoV-MAC-TED’. It consists of unbalanced ROS/RNS levels, which are connected to increased aerobic fermentation that links to alpha-tubulin-based cell restructuration and progression of cell cycle. We conclude that anti-viral/anti-SARS-CoV-2 strategies need to rigorously target ‘CoV-MAC-TED’ in primary infected nose and mouth cells through prophylactic and very early therapeutic strategies. We also discuss potential strategies in the view of the beneficial role of AOX for resilient behavior in plants. Furthermore, following the general observation that ROS/RNS equilibration/redox homeostasis is of utmost importance at the very beginning of viral infection, we highlight that ‘de-stressing’ disease and social handling should be seen as essential part of anti-viral/anti-SARS-CoV-2 strategies.

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  1. Version published to 10.3389/fimmu.2021.673692
  2. Version published to 10.1101/2021.06.08.447491v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.06.08.447491: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationTo confirm the effectiveness of the treatment, few seeds were collected randomly and cut into small pieces.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    BAG4 (AT3G51780.1); BAG5 (AT1G12060.1); BAG6 (AT2G46240.1); BAG7 (AT562390.1)], Meta-caspase (MC-1 (AT1G02170.1); MC-2 (AT4G25110.1) MC-3 (AT5G64240.1); MC-4 (AT1G79340.1); MC-5 (AT1G79330.1); MC-6 (AT1G79320.1); MC-7 (AT1G79310.1); MC-8 (AT1G16420.1); MC-9 (AT5G04200.1)], ASMT (AT4G35160).
    MC-1
    suggested: None
    MC-2
    suggested: None
    MC-4
    suggested: None
    MC-5
    suggested: None
    MC-7
    suggested: None
    MC-9
    suggested: None
    Software and Algorithms
    SentencesResources
    Gene expression was evaluated in specific RNA-seq experiments, which were collected from Sequence Read Archive (SRA) database of GenBank, NCBI.
    Sequence Read Archive
    suggested: (DDBJ Sequence Read Archive, RRID:SCR_001370)
    Specific regions (3’ end) of each cDNA were aligned against RNA-seq experiments using mega BLASTn tool (71) to obtain the mapped reads according to Saraiva et al. (72).
    BLASTn
    suggested: (BLASTN, RRID:SCR_001598)

    Results 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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.06.08.447491v1 on bioRxiv