Nicotine and Covid-19

[King Tryptamine]

I've found a study suggesting the positive role nicotine may or may not have to play in reducing the severity of harm induced by SARS-CoV-2. I have to embarrassingly admit the language used in this study is a little hard for me to understand so please can someone with a better understanding of biology help me out as to what's going on here? What influence does nicotine have on this virus if any? Is the alkaloid somehow reducing the affinity of SARS-CoV-19 towards the ACE-2 receptor? Is it decreasing ACE-2 availability? In general what the hell is going on here?

Smokers being witnessed with the mild adverse clinical symptoms of SARS-CoV-2, the in-silico study is intended to explore the effect of nicotine binding to the soluble angiotensin converting enzyme II (ACE2) receptor with or without SARS-CoV-2 binding. Nicotine established a stable interaction with the conserved amino acid residues: Asp382, Gly405, His378 and Tyr385 through His401 of the soluble ACE2 that seals its interaction with the INS1. Also, nicotine binding has significantly reduced the affinity score of ACE2 with INS1 to -12.6 kcal/mol (versus -15.7 kcal/mol without nicotine) and the interface area to 1933.6 square Angstrom (versus 2057.3 square Angstrom without nicotine). Nicotine exhibited a higher binding affinity score with ACE2-SARS-CoV-2 complex with -6.33 kcal/mol (Vs -5.24 kcal/mol without SARS-CoV-2) and a lowered inhibitory contant value of 22.95 micromolar (Vs 151.69 micromolar without SARS-CoV). Eventhough ACE2 is not a potential receptor for nicotine binding in the healthy people, in COVID19 patients, it may exhibit better binding affinity with the ACE2 receptor. In overall, nicotines strong preference for ACE2-SARS-CoV-2 complex might drastically reduce the SARS-CoV-2 virulence by intervening the ACE2 conserved residues interaction with the spike (S1) protein of SARS-CoV-2.

Edit:Found another study in link 2 suggesting that nicotine decreases ACE-2 availability in multiple organs, however the study then goes on to say this protein is actually more abundant in the lungs of smokers so the effect of nicotine on this virus is still foggy. The same study also makes mention that the alkaloid may decrease covid-19 severity via a cholinergic anti-inflammatory pathway "inhibiting macrophage-driven hyperinflammation and platelet reactivity". Last study I wanna throw out for you guys to read and offer some helpful feedback, is from my limited understanding of this topic the same information given in the second link in which nicotine reduces the severity of covid-19 via the cholinergic pathway.

Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm.

Again I would really like to gain some insight on nicotine's impact on SARS-CoV-2 through your understanding of these studies since I'm finding it quite difficult understanding this science myself, Thanks.

Links:

1 - [2004.14943] A computational insight of the improved nicotine binding with ACE2-SARS-CoV-2 complex with its clinical impact
2 - Beyond Smoking Cessation: Investigating Medicinal Nicotine to Prevent and Treat COVID-19
3 - Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system