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Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein

Maria Fernanda Fernandes, John Zewen Chan, Chia Chun Joey Hung, Michelle Victoria Tomczewski, View ORCID ProfileRobin Elaine Duncan
doi: https://doi.org/10.1101/2022.01.11.475901
Maria Fernanda Fernandes
1University of Waterloo, Department of Kinesiology and Health Sciences, Faculty of Health, 200 University Ave W, BMH 1044, Waterloo, ON, N2L 3G1 Canada
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John Zewen Chan
1University of Waterloo, Department of Kinesiology and Health Sciences, Faculty of Health, 200 University Ave W, BMH 1044, Waterloo, ON, N2L 3G1 Canada
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Chia Chun Joey Hung
1University of Waterloo, Department of Kinesiology and Health Sciences, Faculty of Health, 200 University Ave W, BMH 1044, Waterloo, ON, N2L 3G1 Canada
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Michelle Victoria Tomczewski
1University of Waterloo, Department of Kinesiology and Health Sciences, Faculty of Health, 200 University Ave W, BMH 1044, Waterloo, ON, N2L 3G1 Canada
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Robin Elaine Duncan
1University of Waterloo, Department of Kinesiology and Health Sciences, Faculty of Health, 200 University Ave W, BMH 1044, Waterloo, ON, N2L 3G1 Canada
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  • ORCID record for Robin Elaine Duncan
  • For correspondence: reduncan@uwaterloo.ca
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Abstract

Aims To study effects on cellular innate immune responses to novel genes ORF8 and ORF10, and the more conserved Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, either alone, or in combination with cannabidiol (CBD).

Main Methods HEK293 cells were transfected with a control plasmid, or plasmids expressing ORF8, ORF10, or M protein, and assayed for cell number and markers of apoptosis at 24 h, and expression of interferon and interferon-stimulated genes at 14 h.

Key findings A significant reduction in cell number, and increase in early and late apoptosis, was found after 24 h in cells where expression of viral genes was combined with 1-2 μM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. CBD (2 μM) augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2’-5’-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL, in cells expressing ORF8, ORF10, and M protein. CBD also augmented expression of these genes in control cells not expressing viral genes, without enhancing apoptosis.

Significance Our results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but suggest an augmented innate anti-viral response to these genes in the presence of CBD. Furthermore, our results indicate that CBD may prime components of the innate immune system, increasing readiness to respond to viral infection without activating apoptosis, and therefore could be studied for potential in prophylaxis.

Competing Interest Statement

MFF was a recipient of a Mitacs Accelerate Post-doctoral fellowship award that was funded in part (33%) by Akseera Pharma Corp. MFF and RED are co-inventors on international applications under the Patent Cooperation Treaties entitled "Interaction of Sars-Cov-2 proteins with molecular and cellular mechanisms of host cells and formulations to treat COVID-19" (PCT/IN2021/050325 and PCT/N2021/050699). Akseera Pharma Corp. was not involved in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.

Footnotes

  • Declaration of Conflicting Interests: MFF was a recipient of a Mitacs Accelerate Post-doctoral fellowship award that was funded in part (33%) by Akseera Pharma Corp. MFF and RED are co-inventors on international applications under the Patent Cooperation Treaty entitled “Interaction of Sars-Cov-2 proteins with molecular and cellular mechanisms of host cells and formulations to treat COVID-19” (PCT/IN2021/050325 and PCT/N2021/050699). Akseera Pharma Corp. was not involved in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 12, 2022.
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Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein
Maria Fernanda Fernandes, John Zewen Chan, Chia Chun Joey Hung, Michelle Victoria Tomczewski, Robin Elaine Duncan
bioRxiv 2022.01.11.475901; doi: https://doi.org/10.1101/2022.01.11.475901
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Effect of cannabidiol on apoptosis and cellular interferon and interferon-stimulated gene responses to the SARS-CoV-2 genes ORF8, ORF10 and M protein
Maria Fernanda Fernandes, John Zewen Chan, Chia Chun Joey Hung, Michelle Victoria Tomczewski, Robin Elaine Duncan
bioRxiv 2022.01.11.475901; doi: https://doi.org/10.1101/2022.01.11.475901

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