Abstract
Electronic nicotine delivery systems have recently achieved great popularity as safer alternatives to traditional tobacco. However, there is growing evidence that vaping is not harmless, with documented acute and chronic health effects. This study investigated how components of vape juice interact with human Angiotensin-converting enzyme 2 (ACE2) receptors, using molecular docking, molecular dynamics simulations, and Biolayer Interferometry (BLI). In the initial docking, menthol showed the strongest binding, followed by nicotine and capsaicin, while formaldehyde and acrolein demonstrated moderate binding to the zinc ion binding site of ACE2. Capsaicin formed the greatest number of interactions with multiple hydrogen bonds targeting the catalytic HIS374 residue. Menthol, glycerol, and propylene glycol also formed hydrogen bonds in the active site region, while nicotine formed polar interactions. In contrast, formaldehyde and acrolein, the product of glycerol and propylene glycol, did not form any significant interactions with ACE2, maybe due to their small molecule size. All vaping components formed interactions with the Zn2+ ion, suggesting potential implications on active site functionality. In the BLI experiments, nicotine demonstrated the most stable binding to ACE2, as evidenced by slow dissociation. The binding of menthol and capsaicin to ACE2 was less stable compared to nicotine, possibly due to their hydrophobic nature. These findings can pave the way for future studies exploring the vaping-related effects within a receptor-centric systems biology framework.
Data availability
All relevant data are included in the manuscript or supplementary data. Any additional information is available from authors upon request.
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The authors acknowledge the High-Performance Research Computing Center (HPRC) of Texas A&M University for providing computational resources.
Funding
This work was funded, in part, by the grant from the DHHS-NIH-National Institute of Allergy and Infectious Diseases (NIAID): 5R21AI169046-02; and the Hatch Program, United States Department of Agriculture, National Institute of Food and Agriculture (USDA NIFA): TEX09746.
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Conceptualization, M.D.K. and S.F.; methodology, M.D.K, S.F., S.M. and A.H.; software, S.M., A.N. and M.J.I.; validation, S.M., A.H., S.F. and M.D.K.; formal analysis, S.M.; investigation, S.M., A.N., M.J.I. and A.H.; resources, M.D.K. and S.F.; data curation, S.M.; writing—original draft preparation, S.M. and A.N.; writing—review and editing, S.M., S.F. and M.D.K.; visualization, S.M.; supervision, M.D.K. and S.F.; project administration, M.D.K. and S.F.; funding acquisition, M.D.K. and S.F. All authors have read and agreed to the published version of the manuscript.
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Mallawarachchi, S., Nangia, A., Ibrahim, M.J. et al. Evaluation of molecular interactions of vaping juice components with ACE2 receptor. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39533-0
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DOI: https://doi.org/10.1038/s41598-026-39533-0