Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by N-Acetylcysteine Irrespective of the Oxidoreductive Environment
Sebastiano La Maestra, Silvano Garibaldi, Roumen Balansky, Francesco D’agostini, Rosanna T Micale, Silvio De Flora
Cells, doi:10.3390/cells11203313
The binding of SARS-CoV-2 spikes to the cell receptor angiotensin-converting enzyme 2 (ACE2) is a crucial target both in the prevention and in the therapy of COVID-19. We explored the involvement of oxidoreductive mechanisms by investigating the effects of oxidants and antioxidants on virus uptake by ACE2-expressing cells of human origin (ACE2-HEK293). The cell uptake of pseudoviruses carrying the envelope of either Delta or Omicron variants of SARS-CoV-2 was evaluated by means of a cytofluorimetric approach. The thiol N-acetyl-L-cysteine (NAC) inhibited the uptake of both variants in a reproducible and dose-dependent fashion. Ascorbic acid showed modest effects. In contrast, neither hydrogen peroxide (H 2 O 2 ) nor a system-generating reactive oxygen species (ROS), which play an important role in the intracellular alterations produced by SARS-CoV-2, were able to affect the ability of either Delta or Omicron SARS-CoV-2 pseudoviruses to be internalized into ACE2-expressing cells. In addition, neither H 2 O 2 nor the ROS generating system interfered with the ability of NAC to inhibit that mechanism. Moreover, based on previous studies, a preventive pharmacological approach with NAC would have the advantage of decreasing the risk of developing COVID-19, irrespective of its variants, and at the same time other respiratory viral infections and associated comorbidities.
Author Contributions: Planning, methodology, formal analysis, and editing, S.L.M.; methodology and formal analysis, S.G.; methodology, R.B., F.D. and R.T.M.; supervision, conceptualization, and writing, S.D.F. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding excepting the supply of the materials specified under Acknowledgements.
Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable.
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doi:10.1007/s11845-021-02743-8DOI record:
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