Abstract

A critical step of the SARS-CoV-2 infection is interaction between the SARS-CoV-2 Spike (S) protein’s receptor binding domain on the surface of the viral particle and the ACE2 receptor on the surface of human cells. Thus, the identification of small molecules, antibodies, or other biological molecules that interfere with the formation of the S-ACE2 complex, could help to develop drugs to prevent or treat COVID-19.(1) High-CBD Cannabis treatments show modulation of ACE2 gene expression and ACE2 protein levels in human tissues, but it is unclear if the many cannabimimetic molecules also directly interact with the S-ACE2 binding or if it is merely due to the cannabinoid receptor mediated affects.(2) Additionally, NO likely causes conformational changes on surface glycoproteins that can interfere with host cell fusion, preventing infection and release of virions from already infected host cells, like neuraminidase inhibitors.(3) We will use a RayBio COVID-19 Spike-ACE2 binding assay kit, which is an in vitro enzyme-linked immunosorbent assay, to determine if cannabinoids and terpenes can interfere directly with the S-ACE2 binding, independent of cannabinoid receptors. Additionally, we will determine if NO interferes directly with the RBD of the Spike protein, and if there is a synergistic effect with a formulation of cannabinoids, terpenes, and NO, to give an enhanced interference.

Department

Biological Sciences

Faculty Advisor

Joanna Urban and John Church

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Investigating the Potential for High-CBD Cannabis Sativa and Nitric Oxide to Modulate SARS-CoV-2 Spike-ACE2 Binding

A critical step of the SARS-CoV-2 infection is interaction between the SARS-CoV-2 Spike (S) protein’s receptor binding domain on the surface of the viral particle and the ACE2 receptor on the surface of human cells. Thus, the identification of small molecules, antibodies, or other biological molecules that interfere with the formation of the S-ACE2 complex, could help to develop drugs to prevent or treat COVID-19.(1) High-CBD Cannabis treatments show modulation of ACE2 gene expression and ACE2 protein levels in human tissues, but it is unclear if the many cannabimimetic molecules also directly interact with the S-ACE2 binding or if it is merely due to the cannabinoid receptor mediated affects.(2) Additionally, NO likely causes conformational changes on surface glycoproteins that can interfere with host cell fusion, preventing infection and release of virions from already infected host cells, like neuraminidase inhibitors.(3) We will use a RayBio COVID-19 Spike-ACE2 binding assay kit, which is an in vitro enzyme-linked immunosorbent assay, to determine if cannabinoids and terpenes can interfere directly with the S-ACE2 binding, independent of cannabinoid receptors. Additionally, we will determine if NO interferes directly with the RBD of the Spike protein, and if there is a synergistic effect with a formulation of cannabinoids, terpenes, and NO, to give an enhanced interference.

 

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