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

• Published in: Free radical biology & medicine Vol. 161; pp. 263 - 271
• Main Authors: Singh, Devendra, Wasan, Himika, Reeta, K.H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020
• Subjects: Antiviral activity; Antiviral Agents - metabolism; Coagulopathy; COVID-19; COVID-19 - immunology; COVID-19 Drug Treatment; Disseminated Intravascular Coagulation - prevention & control; Fibrinolytic Agents - metabolism; Heme - metabolism; Heme Oxygenase-1; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; HO-1 promoter polymorphism; Humans; Hypothesis Paper; Inflammation; Interferon Type I - immunology; Polymorphism, Single Nucleotide - genetics; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - growth & development; Type-1 IFNs; COVID-19; HO-1 promoter polymorphism; SARS-CoV-2; Antiviral activity; Type-1 IFNs; Heme Oxygenase-1; Inflammation; Coagulopathy
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.10.016

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. [Display omitted] •COVID-19 causes significant mortality and needs urgent treatment strategies.•SARS-CoV-2 inhibits interferons (IFN) and increased IFNs suppresses its replication.•Heme oxygenase-1 (HO-1) inducers suppress viral replication by increasing IFNs.•HO-1 promoter polymorphisms modulate disease severity, which may be true in COVID-19.•Inflammation and coagulopathies seen in COVID-19 can be controlled by inducing HO-1.