**A Journey into the Clinical Relevance of Heme Oxygenase 1 for Human Inflammatory Disease and Viral Clearance: Why Does It Matter on the COVID-19 Scene?**

**Ayelen Toro 1,2,\*, María Sol Ruiz 1,2, Sofia Lage-Vickers 1,2, Pablo Sanchis 1,2, Agustina Sabater 1,2, Gaston Pascual 1,2, Rocio Seniuk 1,2, Florencia Cascardo 1,2, Sabrina Ledesma-Bazan 1,2, Felipe Vilicich 1,2, Elba Vazquez 1,2 and Geraldine Gueron 1,2,\***


**Abstract:** Heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, is involved in the maintenance of cellular homeostasis, exerting a cytoprotective role by its antioxidative and anti-inflammatory functions. HO-1 and its end products, biliverdin, carbon monoxide and free iron (Fe2+), confer cytoprotection against inflammatory and oxidative injury. Additionally, HO-1 exerts antiviral properties against a diverse range of viral infections by interfering with replication or activating the interferon (IFN) pathway. Severe cases of coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are characterized by systemic hyperinflammation, which, in some cases, leads to severe or fatal symptoms as a consequence of respiratory failure, lung and heart damage, kidney failure, and nervous system complications. This review summarizes the current research on the protective role of HO-1 in inflammatory diseases and against a wide range of viral infections, positioning HO-1 as an attractive target to ameliorate clinical manifestations during COVID-19.

**Keywords:** heme oxygenase 1; COVID-19; influenza A virus; respiratory syncytial virus; human immunodeficiency virus; Ebola virus; Dengue virus; Zika virus; Hepatitis virus; SARS-CoV-2
