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Sci Rep ; 11(1): 21462, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500517

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.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Heme Oxygenase-1/metabolism , Hemin/therapeutic use , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/virology , Cell Survival/drug effects , Chlorocebus aethiops , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/genetics , Hemin/chemistry , Hemin/pharmacology , 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
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