Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H₂S donors in COVID‐19 therapy

Abstract

The COVID-19 pandemic caused by SARS-Cov-2 demands rapid, safe and effective therapeutic options. In the last decades, the endogenous gasotransmitter hydrogen sulfide (H 2 S) has emerged as modulator of several biological functions and its deficiency has been associated with different disorders. Therefore, many H 2 S-releasing agents have been developed as potential therapeutic tools for diseases related with impaired H 2 S production and/or activity. Some of these compounds are in advanced clinical trials. Presently, the pivotal role of H 2 S in modulating the inflammatory response and pro-inflammatory cytokine cascade is well recognized, and the usefulness of some H 2 S-donors for the treatment of acute lung inflammation has been reported. Recent data is elucidating several mechanisms of action, which may account for antiviral effects of H 2 S. Noteworthy, some preliminary clinical results suggest an inverse relationship between endogenous H 2 S levels and severity of COVID-19. Therefore, repurposing of H 2 S-releasing drugs may be a potential therapeutic opportunity for treatment of COVID-19.

Decreased availability of nitric oxide and hydrogen sulfide is a hallmark of COVID-19

“…NO acts as a vasodilator and an antiviral agent in patients with SARS and can inhibit in vitro replication of SARS-CoV-2 [9 , 10] . While several recent reviews also suggest an association between H 2 S and SARS-CoV-1/2, they provide little evidence of any of such relationship[ [11] , [12] , [13] , [14] ]. Consistent with these suppositions is the possibility that endothelial dysfunction concomitant with COVID-19 infection is likely to result in reduced NO and H 2 S metabolite availability.…”

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

“…Since endothelial dysfunction and inflammation continue to be the main causes of morbidity and mortality all over the world, knowledge of the molecular and biochemical mechanisms underlying cardiovascular pathologies and their complications is still required, as well as the definition of new treatment options to prevent endothelial dysfunction or revert cardiovascular disorders [ 183 , 184 ]. The recent pandemic evidenced this unresolved medical need [ 185 ].…”

Fluidics System for Resolving Concentration-Dependent Effects of Dissolved Gases on Tissue Metabolism

“…Although it is possible that in vivo, tissue is much less sensitive to H 2 S than in vitro, it seems more likely that assays that measure plasma H 2 S result in a significant overestimate coming from related sulfur-containing compounds. The ability to detect differences between responses to H 2 S and donor molecules, will be useful to the increasing numbers of investigators developing H 2 S donor molecules as pharmaceutics 67, 68 . The increase in ISR in response to H 2 S has physiological, methodological and clinical implications and the lack of similar stimulatory effects by a donor molecule has broad implications in a field where studies of NO, H 2 S and CO are mostly based on the use of donor molecules.…”