Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications

Free Radic Biol Med. 2020 Dec:161:263-271. doi: 10.1016/j.freeradbiomed.2020.10.016. Epub 2020 Oct 19.

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to infect hundred thousands of people every day worldwide. Since it is a novel virus, research continues to update the possible therapeutic targets when new evidence regarding COVID-19 are gathered. This article presents an evidence-based hypothesis that activating the heme oxygenase-1 (HO-1) pathway is a potential target for COVID-19. Interferons (IFNs) have broad-spectrum antiviral activity including against SARS-CoV-2. Induction of HO-1 and increase in the heme catabolism end-product confer antiviral activity. IFN activation results in inhibition of viral replication in various viral infections. COVID-19 induced inflammation as well as acute respiratory distress syndrome (ARDS), and coagulopathies are now known major causes of mortality. A protective role of HO-1 induction in inflammation, inflammation-induced coagulation, and ARDS has been reported. Based on an association of HO-1 promoter polymorphisms and disease severity, we propose an evaluation of the status of these polymorphisms in COVID-19 patients who become severely ill. If an association is established, it might be helpful in identifying patients at high risk. Hence, we hypothesize that HO-1 pathway activation could be a therapeutic strategy against COVID-19 and associated complications.

Keywords: Antiviral activity; COVID-19; Coagulopathy; HO-1 promoter polymorphism; Heme Oxygenase-1; Inflammation; SARS-CoV-2; Type-1 IFNs.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / metabolism
  • COVID-19 / immunology*
  • COVID-19 Drug Treatment
  • Disseminated Intravascular Coagulation / prevention & control
  • Fibrinolytic Agents / metabolism*
  • Heme / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Interferon Type I / immunology*
  • Polymorphism, Single Nucleotide / genetics
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / growth & development*

Substances

  • Antiviral Agents
  • Fibrinolytic Agents
  • Interferon Type I
  • Heme
  • HMOX1 protein, human
  • Heme Oxygenase-1