Anti‐inflammatory and antiviral roles of hydrogen sulfide: rationale for considering H(2)S‐donors in COVID‐19 therapy

Citi, Valentina; Martelli, Alma; Brancaleone, Vincenzo; Brogi, Simone; Gojon, Gabriel; Montanaro, Rosangela; Morales, Guillermo; Testai, Lara; Calderone, Vincenzo

The COVID‐19 pandemic caused by new betacoronavirus SARS‐Cov‐2 demands rapid exploration of safe and effective therapeutic options. In this perspective, “drug repurposing” aims to represent a rapid and valuable strategy. In the last decades, the endogenous gasotransmitter hydrogen sulfide (H(2)S) has emerged as a ubiquitous modulator of several biological functions. Early studies pointed out its importance in the regulation of numerous biological functions and systems. Accordingly, H(2)S deficiency has been associated with several disorders, and many chemotypes of H(2)S‐releasing agents have been developed as potential therapeutic tools for diseases related with impaired H(2)S production/activity. Some of these compounds are in advanced clinical trials. Presently, the pivotal role of H(2)S in modulating the inflammatory response and proinflammatory cytokine cascade is well recognized, and the usefulness of some H(2)S‐donors for the treatment of different forms of acute lung inflammation (due to infectious and non‐infectious etiologies) has been reported. More recent evidence is also unravelling several mechanisms of action which may account for antiviral effects of this gasotransmitter. Noteworthy, some preliminary clinical results suggest an inverse relationship between endogenous H(2)S levels and severity of COVID‐19 disease. Therefore, repurposing of H(2)S‐releasing drugs may be worthy of investigation as potential therapeutic opportunities for treatment of COVID‐19 disease.