Smoking is a harmful habit that makes us vulnerable to many diseases – Is it the same with Covid-19 infection or does cigarette smoke work “protectively”?
Japanese researchers say they have found an answer to a scientific paradox regarding the susceptibility of smokers to Covid-19 infection.
Studies have shown that while smokers are more vulnerable to respiratory infections – and consequently to the disease caused by SARS-CoV-2 – but at the same time the rates of smokers with coronavirus are less compared to non-smokers.
According to an article published in Scientific Reports, Keiji Tanimoto’s scientific team at the University of Hiroshima has discovered two active substances that mimic the effects of chemicals contained in cigarette smoke and bind to a receptor in the cells of all mammalian species that inhibit production of ACE2 proteins, a process that appears to reduce the ability of the coronavirus to invade cells.
It is well known that cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs), which bind and activate aryl hydrocarbon receptors (AHRs). These are receptors within cells that are also a transcription factor, meaning they can trigger a wide range of cellular activities through their ability to increase or decrease the expression of specific genes.
Knowing the relationship between PAHs and AHRs, the researchers wanted to study the effect of active ingredients that activate AHRs on the expression of genes that control the production of ACE2 protein – the infamous receptor protein on the surface of many cell types that acts as the “key” the SARS-CoV-2 virus is able to unlock. Once the virus manages to “stick” to the ACE2 protein, it can then enter and infect the cell.
Scientists first studied various cell lines to look at ACE2 gene expression levels. They, therefore, observed that cells from the oral cavity, lungs and liver had the highest expression rates of this protein.
These cells were then exposed to various doses of a cigarette smoke extract for 24 hours. The expression rate of the CYP1A1 gene was then assessed. Indeed, its exposure to tobacco extract caused its increased expression in liver and lung cells in a dose-dependent manner. However, the same was not observed in the cells of the oral cavity. In other words, the higher the activity of CYP1A1 the lower the production of ACE2 receptors.
Using RNA sequencing, the researchers looked at what exactly happened to gene expression and found that cigarette smoke extract increased the expression of genes involved in a number of key signaling processes within cells regulated by arylate hydrogen receptor (AHR) receptors.
And to more closely monitor this mechanism by which AHRs act on ACE2 expression, they studied the effect of two drugs that activate AHRs on liver cells. The first was a tryptophan derivative and the second, omeprazole, which is widely used in the treatment of gastroesophageal reflux disease and peptic ulcers.
Data from the RNA sequence showed that the CYP1A1 gene penetrated deep into the liver cells thanks to AHRs and the expression of the ACE2 gene was silenced, again in a dose-dependent manner.
Simply put, cigarette smoke extract and the two drugs mentioned above can suppress ACE2 expression in cells and thus reduce the ability of SARS-CoV-2 to enter cells.
These findings pave the way for clinical trials of drugs as candidate therapies for Covid-19 infection.
