ABSTRACT
The inducible cytoprotective enzyme heme oxygenase-1 (HO-1) has gained significant recognition in recent years for mediating strong cellular resistance to a broad range of viral infections, regardless of the type of viruses, viral strains, or mutants. HO-1 is not a typical antiviral agent that targets any particular pathogen. It is a "viral tropism independent" endogenous host defense factor that upon induction provides general cellular protection against pathogens. By virtue of HO-1 being widely distributed intracellular enzyme in virtually every cell, this unique host factor presents a novel class of generic host defense system against a variety of viral infections. This Viewpoint proposes pharmacological evaluation of the HO-1-dependent cellular resistance for its potential in mitigating infections by deadly viruses, including the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its variants, and mutants. HO-1-dependent cellular resistance against SARS-CoV-2 can complement current medical modalities for much effective control of the COVID-19 pandemic, especially with constantly emerging new viral variants and limited therapeutic options to treat SARS-CoV-2 infection and associated severe health consequences.