Abstract
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.
Keywords: COVID-19; N-acetyl-L-cysteine; SARS-CoV-2; ascorbic acid; cell internalization; hydrogen peroxide; reactive oxygen species.
【저자키워드】 COVID-19, SARS-CoV-2, hydrogen peroxide, ascorbic acid, Reactive oxygen species., cell internalization, N-acetyl-L-cysteine, 【초록키워드】 ACE2, therapy, variant, Comorbidities, Delta, risk, omicron, antioxidant, angiotensin-converting enzyme 2, variants, ROS, mechanism, respiratory viral infection, reactive oxygen species, binding, SARS-CoV-2 spike, Previous studies, alteration, ACE2-expressing cells, pharmacological, variants of SARS-CoV-2, Effect, Affect, Effects, approach, Cell, cell receptor, NAC, produced, addition, inhibit, evaluated, inhibited, dose-dependent, reactive oxygen specy, ACE2-expressing cell, Oxidant, pseudovirus, SARS-CoV-2 pseudovirus, virus uptake, 【제목키워드】 Delta, inhibition, omicron, Environment, N-acetylcysteine, uptake,