Utility of NO and H(2)S donating platforms in managing COVID-19: Rationale and promise

Viral infections are a continuing global burden on the human population, underscored by the ramifications of the COVID-19 pandemic. Current treatment options and supportive therapies for many viral infections are relatively limited, indicating a need for alternative therapeutic approaches. Virus-induced damage occurs through direct infection of host cells and inflammation-related changes. Severe cases of certain viral infections, including COVID-19, can lead to a hyperinflammatory response termed cytokine storm, resulting in extensive endothelial damage, thrombosis, respiratory failure, and death. Therapies targeting these complications are crucial in addition to antiviral therapies. Nitric oxide and hydrogen sulfide are two endogenous gasotransmitters that have emerged as key signaling molecules with a broad range of antiviral actions in addition to having anti-inflammatory properties and protective functions in the vasculature and respiratory system. The enhancement of endogenous nitric oxide and hydrogen sulfide levels thus holds promise for managing both early-stage and later-stage viral infections, including SARS-CoV-2. Using SARS-CoV-2 as a model for similar viral infections, here we explore the current evidence regarding nitric oxide and hydrogen sulfide's use to limit viral infection, resolve inflammation, and reduce vascular and pulmonary damage.