Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients

Eur J Pharmacol. 2021 Sep 15:907:174306. doi: 10.1016/j.ejphar.2021.174306. Epub 2021 Jul 7.

Abstract

The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P < 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P < 0.001) and post-treatment measurements (P < 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.

Keywords: Antiviral therapy; COVID-19; Disulfide; Nitric oxide; Thiol.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • COVID-19 / blood*
  • COVID-19 Drug Treatment*
  • Disulfides / blood*
  • Female
  • Homeostasis
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / blood*
  • SARS-CoV-2*
  • Sulfhydryl Compounds / blood*

Substances

  • Antiviral Agents
  • Disulfides
  • Sulfhydryl Compounds
  • Nitric Oxide