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

Author links open overlay panel Devendra Singh Himika Wasan K.H.Reeta

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India

Highlights

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.

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.

Graphical abstract