Possible application of H 2 S-producing compounds in therapy of coronavirus (COVID-19) infection and pneumonia
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LETTER TO THE EDITOR
Possible application of H2S-producing compounds in therapy of coronavirus (COVID-19) infection and pneumonia Mikhail B. Evgen’ev 1 & Anton Frenkel 2
# Cell Stress Society International 2020
In recent years, the gasotransmitter hydrogen sulfide (H2S) has been recognized as a biological mediator of immense importance both in eukaryotes and prokaryotes (Kimura 2014; Xiao et al. 2018). H2S is produced in the cells mostly through the reverse transsulfuration pathway (TSP). Transsulfuration is a vital metabolic process common in prokaryotes and eukaryotes that have been studied in detail in mammals including human and several other organisms. It has been demonstrated by different groups that defects in the H2S synthesizing enzyme system are involved in a plethora of diseases in humans including cancer and a number of neurodegenerative diseases (Wallace and Wang 2015; Bhattacharyya et al. 2016). Although at high concentration H2S is a poison, at low concentrations, it elicits cytoprotection during oxidative stress by decreasing reactive oxygen species (ROS) production in a wide range of physiologic and pathologic conditions (Kaya-Yasar et al. 2017; Faller et al. 2018). It is interesting that cysteine is sulfur-rich and likely involved as a modulator of ROS due to S–S bonds. To this end, sulfide-rich water in baths is routinely used in sanatoriums to treat multiple diseases. In recent decades, we studied the effects of endogenous and exogenous hydrogen sulfide at the cellular and organism levels (Yurinskaya et al. 2020; Shilova et al. 2020; Zatsepina et al. in press). In our investigation, we explored slow- and fast-releasing H2S donors as well as deletions of the genes responsible for H2S production and demonstrated a strong anti-inflammatory effect of this gas which ameliorates various manifestations of inflammation including ROS, NO, TNF-α, and interleukin-6.
* Mikhail B. Evgen’ev [email protected] 1
Laboratory of Molecular Mechanisms of Biological Adaptations, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 119991
2
Clexio Biosciences Ltd., Petah-Tikva, Israel
Along these lines, there are studies demonstrating antiviral and anti-inflammatory activity of H2S in several rodent models (Bazhanov et al. 2018; Bazhanov et al. 2017). In an animal model, hydrogen sulfide donors are usually introduced by inhalation to efficiently alleviate lung injury and pneumonia induced by bacteria or viruses (Zhang et al. 2019; Sakaguchi et al. 2014; Kakinohana et al. 2019). It was also shown in rodent models that pre- and posttreatment with hydrogen sulfide prevents ventilator-induced lung injury by limiting inflammation and oxidation (Faller et al. 2017). Since hydrogen sulfide is a toxic gas, its use “as is” for inhalation is problematic. Water-soluble sulfide salts such as Na2S and NaHS generate free H2S in aqueous solutions. Thus, diluted solutions of inorganic sulfides could be used for inhalation with a nebulizer, but an important drawback of these compounds is t
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