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Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by N-Acetylcysteine Irrespective of the Oxidoreductive Environment

Title: Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by N-Acetylcysteine Irrespective of the Oxidoreductive Environment
Authors: Sebastiano La Maestra; Silvano Garibaldi; Roumen Balansky; Francesco D’Agostini; Rosanna T. Micale; Silvio De Flora
Contributors: LA MAESTRA, Sebastiano; Garibaldi, Silvano; Balansky, Roumen; D’Agostini, Francesco; Micale, Rosanna T.; DE FLORA, Silvio
Publisher Information: MDPI; CHE; ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
Publication Year: 2022
Collection: Università degli Studi di Genova: CINECA IRIS
Subject Terms: COVID-19; N-acetyl-L-cysteine; SARS-CoV-2; ascorbic acid; cell internalization; hydrogen peroxide; reactive oxygen species; Humans; Acetylcysteine; Antioxidants; HEK293 Cells; Peptidyl-Dipeptidase A; Oxidants; Sulfhydryl Compounds; Angiotensin-Converting Enzyme 2
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 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 (H2O2) 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 H2O2 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.
Document Type: article in journal/newspaper
File Description: ELETTRONICO
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/36291178; info:eu-repo/semantics/altIdentifier/wos/WOS:000872421000001; volume:11(20); firstpage:3313-1; lastpage:3313-13; numberofpages:13; journal:CELLS; https://hdl.handle.net/11567/1099224
DOI: 10.3390/cells11203313
Availability: https://hdl.handle.net/11567/1099224; https://doi.org/10.3390/cells11203313
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.B2AF278F
Database: BASE