SARS-CoV-2, ACE2 – Hypothesis #1

Came across this tweet by Dr Bertrand Dautzenberg a few days ago.

Nice remark about the incidence of COVID-19 in populations of smokers, ex-smokers and non-smokers, the trent being counter-intuitive (well, at least for any tabacologist ready to diabolise smokers!). Data are from Clinical Characteristics of Coronavirus Disease 2019 in China.


 Obviously ex-smokers seems to be less affected than smokers and the prevalence is much higher for non-smokers. Most of the comments I had read up to this point were pessimistic for smokers who were considered at higher risk.

One of the reasons is that tobacco consumption seems to stimulate the expression of the cellular receptor for the virus, ACE2. My first reaction was related to the cell types that express the receptor. Guys with some work on cystic fibrosis can have such misguided first impression when it comes to lungs. Now I think it was a bad reaction, the molecular biologist beating the cellular biologist (any day!)

A PubMed ace2 expression lung brings two douzains of papers  (8 Apr 2020) and easy read at the abstract level with <53k words. So I read them and its’s an interesting way to spend lockdown.

There is a trend: the more ACE2 one produces the less susceptible he seems to be to infection by SARS-CoV-2, or if infected the less severe the disease.

Males produce less than females, older individuals less than youngsters, non-smokers less than smokers, them less than ex-smokers. The less you produce the more you are threatened by the virus.


ACE2 is the cellular receptor, situated on the plasma membrane and acts by binding the spike of the virion, giving it a proteolytic cut to produce two fragments, one of which will promote the fusion of the viral and cell membranes resulting to the entry of the virus in the cell. 
Everybody heard of that nowadays.


ACE2 is far from being strictly associated to the cells membrane. The extracellular part of the protein, interacting with the virus, is liberated in the extracellular space and it will make its way to the blood.
The more you produce, the more you will have in the extracellular space! That is the space the virus have to cross to reach the cell membrane. Poor virion have to go through a mined territory, with proteases splitting its spikes? Well, That<s the question to ask: does free ACE2 acts on SARS-CoV-2 spike by degrading it and thus inhibiting the entry of the virions in cells?

And that/s a nice question as the affirmative will give a way to deal with COVID19.

And just before reviewer #1 answers via Skype, I’ll hit “send”

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