Your browser doesn't support javascript.
SARS-CoV2 infection impairs the metabolism and redox function of cellular glutathione.
Bartolini, Desirée; Stabile, Anna Maria; Bastianelli, Sabrina; Giustarini, Daniela; Pierucci, Sara; Busti, Chiara; Vacca, Carmine; Gidari, Anna; Francisci, Daniela; Castronari, Roberto; Mencacci, Antonella; Di Cristina, Manlio; Focaia, Riccardo; Sabbatini, Samuele; Rende, Mario; Gioiello, Antimo; Cruciani, Gabriele; Rossi, Ranieri; Galli, Francesco.
  • Bartolini D; Department of Pharmaceutical Sciences, University of Perugia, Nutrition and Clinical Biochemistry Lab, Via Del Giochetto, Monteluce, Perugia, Italy; Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, School of Medicine, University of Perugia, P.le Lucio Severi, 1, S
  • Stabile AM; Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, School of Medicine, University of Perugia, P.le Lucio Severi, 1, Sant'Andrea Delle Fratte, 06132, Perugia, Italy.
  • Bastianelli S; Department of Medicine and Surgery, Clinic of Infectious Diseases, University of Perugia, Perugia, Italy.
  • Giustarini D; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, I-53100, Siena, Italy.
  • Pierucci S; Department of Medicine and Surgery, Clinic of Infectious Diseases, University of Perugia, Perugia, Italy.
  • Busti C; Department of Medicine and Surgery, Clinic of Infectious Diseases, University of Perugia, Perugia, Italy.
  • Vacca C; Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123, Perugia, Italy.
  • Gidari A; Department of Medicine and Surgery, Clinic of Infectious Diseases, University of Perugia, Perugia, Italy.
  • Francisci D; Department of Medicine and Surgery, Clinic of Infectious Diseases, University of Perugia, Perugia, Italy.
  • Castronari R; Department of Medicine and Surgery, Microbiology Unit, University of Perugia, 06123, Perugia, Italy.
  • Mencacci A; Department of Medicine and Surgery, Microbiology Unit, University of Perugia, 06123, Perugia, Italy.
  • Di Cristina M; Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123, Perugia, Italy.
  • Focaia R; Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123, Perugia, Italy.
  • Sabbatini S; Department of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06129, Perugia, Italy.
  • Rende M; Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, School of Medicine, University of Perugia, P.le Lucio Severi, 1, Sant'Andrea Delle Fratte, 06132, Perugia, Italy.
  • Gioiello A; Department of Pharmaceutical Sciences, University of Perugia, Nutrition and Clinical Biochemistry Lab, Via Del Giochetto, Monteluce, Perugia, Italy.
  • Cruciani G; Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123, Perugia, Italy.
  • Rossi R; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, I-53100, Siena, Italy.
  • Galli F; Department of Pharmaceutical Sciences, University of Perugia, Nutrition and Clinical Biochemistry Lab, Via Del Giochetto, Monteluce, Perugia, Italy. Electronic address: francesco.galli@unipg.it.
Redox Biol ; 45: 102041, 2021 09.
Article in English | MEDLINE | ID: covidwho-1263367
ABSTRACT
Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were investigated for the first time in SARS-CoV2-infected Vero E6 cells, a reliable and well-characterized in vitro model of this infection. SARS-CoV2 markedly decreased the levels of cellular thiols, essentially lowering the reduced form of glutathione (GSH). Such an important defect occurred early in the CPE process (in the first 24 hpi). Thiol analysis in N-acetyl-Cys (NAC)-treated cells and membrane transporter expression data demonstrated that both a lowered uptake of the GSH biosynthesis precursor Cys and an increased efflux of cellular thiols, could play a role in this context. Increased levels of oxidized glutathione (GSSG) and protein glutathionylation were also observed along with upregulation of the ER stress marker PERK. The antiviral drugs Remdesivir (Rem) and Nelfinavir (Nel) influenced these changes at different levels, essentially confirming the importance or blocking viral replication to prevent GSH depletion in the host cell. Accordingly, Nel, the most potent antiviral in our in vitro study, produced a timely activation of Nrf2 transcription factor and a GSH enhancing response that synergized with NAC to restore GSH levels in the infected cells. Despite poor in vitro antiviral potency and GSH enhancing function, Rem treatment was found to prevent the SARS-CoV2-induced glutathionylation of cellular proteins. In conclusion, SARS-CoV2 infection impairs the metabolism of cellular glutathione. NAC and the antiviral Nel can prevent such defect in vitro.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Glutathione Limits: Humans Language: English Journal: Redox Biol Year: 2021 Document Type: Article

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Glutathione Limits: Humans Language: English Journal: Redox Biol Year: 2021 Document Type: Article