Hemin as a novel candidate for treating COVID-19 via heme oxygenase-1 induction

Sci Rep. 2021 Nov 2;11(1):21462. doi: 10.1038/s41598-021-01054-3.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Hemin / chemistry
  • Hemin / pharmacology
  • Hemin / therapeutic use*
  • Humans
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • RNA, Viral / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / physiology
  • Up-Regulation / drug effects
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • RNA, Small Interfering
  • RNA, Viral
  • Hemin
  • Heme Oxygenase-1