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.
