Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment
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 b...
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/20/3313 |
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| author | Sebastiano La Maestra Silvano Garibaldi Roumen Balansky Francesco D’Agostini Rosanna T. Micale Silvio De Flora |
| author_facet | Sebastiano La Maestra Silvano Garibaldi Roumen Balansky Francesco D’Agostini Rosanna T. Micale Silvio De Flora |
| author_sort | Sebastiano La Maestra |
| collection | DOAJ |
| description | 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 <i>N</i>-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<sub>2</sub>O<sub>2</sub>) 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<sub>2</sub>O<sub>2</sub> 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. |
| first_indexed | 2024-03-09T20:28:08Z |
| format | Article |
| id | doaj.art-536514fb0b834cbb8804248d288e7582 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:28:08Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-536514fb0b834cbb8804248d288e75822023-11-23T23:29:01ZengMDPI AGCells2073-44092022-10-011120331310.3390/cells11203313Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive EnvironmentSebastiano La Maestra0Silvano Garibaldi1Roumen Balansky2Francesco D’Agostini3Rosanna T. Micale4Silvio De Flora5Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, ItalyDepartment of Internal Medicine and Medical Specialties (DIMI), University of Genoa, 16132 Genoa, ItalyNational Centre of Oncology, 1756 Sofia, BulgariaDepartment of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, ItalyDepartment of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, ItalyDepartment of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, ItalyThe 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 <i>N</i>-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<sub>2</sub>O<sub>2</sub>) 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<sub>2</sub>O<sub>2</sub> 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.https://www.mdpi.com/2073-4409/11/20/3313SARS-CoV-2COVID-19cell internalization<i>N</i>-acetyl-L-cysteineascorbic acidhydrogen peroxide |
| spellingShingle | Sebastiano La Maestra Silvano Garibaldi Roumen Balansky Francesco D’Agostini Rosanna T. Micale Silvio De Flora Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment Cells SARS-CoV-2 COVID-19 cell internalization <i>N</i>-acetyl-L-cysteine ascorbic acid hydrogen peroxide |
| title | Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment |
| title_full | Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment |
| title_fullStr | Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment |
| title_full_unstemmed | Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment |
| title_short | Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by <i>N</i>-Acetylcysteine Irrespective of the Oxidoreductive Environment |
| title_sort | inhibition of the cell uptake of delta and omicron sars cov 2 pseudoviruses by i n i acetylcysteine irrespective of the oxidoreductive environment |
| topic | SARS-CoV-2 COVID-19 cell internalization <i>N</i>-acetyl-L-cysteine ascorbic acid hydrogen peroxide |
| url | https://www.mdpi.com/2073-4409/11/20/3313 |
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