Cysteamine with In Vitro Antiviral Activity and Immunomodulatory Effects Has the Potential to Be a Repurposing Drug Candidate for COVID-19 Therapy

Cells. 2021 Dec 24;11(1):52. doi: 10.3390/cells11010052.

Abstract

The ongoing pandemic of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), needs better treatment options both at antiviral and anti-inflammatory levels. It has been demonstrated that the aminothiol cysteamine, an already human applied drug, and its disulfide product of oxidation, cystamine, have anti-infective properties targeting viruses, bacteria, and parasites. To determine whether these compounds exert antiviral effects against SARS-CoV-2, we used different in vitro viral infected cell-based assays. Moreover, since cysteamine has also immune-modulatory activity, we investigated its ability to modulate SARS-CoV-2-specific immune response in vitro in blood samples from COVID-19 patients. We found that cysteamine and cystamine decreased SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6 cells. Interestingly, the antiviral action was independent of the treatment time respect to SARS-CoV-2 infection. Moreover, cysteamine and cystamine significantly decreased viral production in Vero E6 and Calu-3 cells. Finally, cysteamine and cystamine have an anti-inflammatory effect, as they significantly decrease the SARS-CoV-2 specific IFN-γ production in vitro in blood samples from COVID-19 patients. Overall, our findings suggest that cysteamine and cystamine exert direct antiviral actions against SARS-CoV-2 and have in vitro immunomodulatory effects, thus providing a rational to test these compounds as a novel therapy for COVID-19.

Keywords: COVID-19; SARS-CoV-2; antiviral; cystamine; cysteamine; drug repurposing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antiviral Agents / pharmacology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cystamine / pharmacology
  • Cysteamine / pharmacology*
  • Cystine Depleting Agents / pharmacology
  • Drug Repositioning / methods*
  • Female
  • Humans
  • Immunomodulating Agents / pharmacology*
  • Male
  • Middle Aged
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology
  • Vero Cells
  • Virus Replication / drug effects
  • Virus Replication / genetics

Substances

  • Antiviral Agents
  • Cystine Depleting Agents
  • Immunomodulating Agents
  • RNA, Viral
  • Cysteamine
  • Cystamine