Lung diseases and viral infections

Lung viral infections

H₂S is a main human natural defence against infections of the airways from viruses. Studies on the Respiratory Sincitial Virus (RSV) and other paramyxovirus infections in airway epithelial cells showed that the early phase of the infection associates with reduced release and intracellular level of H₂S. The inhibition of a H₂S production further promoted viral replication whereas the application of H₂S reduced pro-inflammatory mediators production and viral replication. These mechanisms were confirmed on an array of enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families including all the influenza virus strains tested (H1N1, H3N2 and Brisbane strain). Accordingly, H₂S modulation was proposed as an approach for broad spectrum antiviral treatments.

SARS-CoV-2, responsible for Covid 19 epidemic, is as well an encapsulated RNA virus and might respond to the same mechanisms. Indeed, in Covid 19 patients the serum concentration of H₂S is higher in survivors compared to fatal cases and correlates with the level of IL-6 and with mortality. Several authors have proposed H₂S as an opportunity for therapeutic inteventions in Covid 19 and a full explanation of the disease as consequence of viral-induced drop of H₂S has been proposed. Briefly, H₂S is able to keep open the K_ATP channels of leucocytes, which avoids endothelial adhesion and cytokine storm essential to viral replication and disease pathogenesis. The virus is able to block this mechanism allowing its own replication and multiple organ damages. Fertile women and younger people, enjoying better efficient H₂S release, are better protected from the infection but genetic weaknesses may cause overt disease in any subjects.

References

Li H et al. Role of Hydrogen Sulfide in Paramyxovirus Infections. J Virol. 2015;89(10):5557–5568. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442521/#:~:text=This%20study%20identifies%20hydrogen%20sulfide,novel%20therapeutic%20approaches%20for%20viral

Ivanciuc T et al. Hydrogen Sulfide Is an Antiviral and Antiinflammatory Endogenous Gasotransmitter in the Airways. Am J Respir Cell Mol Biol 2016; 55(5): 684–696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105180/

Bazhanov N et al. Broad-Range Antiviral Activity of Hydrogen Sulfide Against Highly Pathogenic RNA Viruses. Sci Rep. 2017;7:41029. https://www.nature.com/articles/srep41029

Bazhanov N et al. Thiol-Activated Hydrogen Sulfide Donors Antiviral and Anti-Inflammatory Activity in Respiratory Syncytial Virus Infection Viruses. 2018 May; 10(5): 249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977242/

Renieris G, Katrini K, Damoulari C, Akinosoglou K, Psarrakis C, Kyriakopoulou M, et al. Serum Hydrogen Sulfide and Outcome Association in Pneumonia by the SARS-CoV-2 Corona Virus. Shock 2020, doi: 0.1097/SHK.0000000000001562. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363385/

Yang G. H₂S as a potential defense against COVID-19? Am J Physiol Cell Physiol 2020 Aug 1;319(2):C244-C249. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381713/

Evgen’ev MB & Frenkel A. Possible application of H2S-producing compounds in therapy of coronavirus (COVID-19) infection and pneumonia. Cell Stress & Chaperones, 14 May 2020. https://europepmc.org/article/pmc/pmc7221330

Citi V et al. Anti-inflammatory and antiviral roles of hydrogen sulfide: rationale for considering H2Sdonors in COVID-19 therapy. Br J Pharmacol 2020 Aug 11 : 10.1111/bph.15230. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436626/ 

Dattilo M. Role of host defences in Covid 19 and treatments thereof. Mol Med 2020; 26:90. https://molmed.biomedcentral.com/articles/10.1186/s10020-020-00216-9

Asthma

The same mechanisms above described, including the effect on K_ATP channels, is also responsible for bronchodilation and an hampered release is involved in the pathogenesis of asthma.

Indeed, the H₂S producing enzymes CSE and CBS are well expressed in smooth muscle cells and endothelial cells of pulmonary blood vessels. Compared to unaffected subjects, asthma patients have decreased blood levels of H₂S that further drop during asthmatic crisis. Experimental animal models demonstrate an abnormal metabolism of H₂S in asthma with deficit of release associated to bronchospasm, airway remodeling and chronic inflammation, which can be improved by H₂S donors.

References

Wang P et al. Hydrogen sulfide and asthma. Exp Physiol 96.9 pp 847–852. https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2011.057448

Hatziefthimiou A & Stamatiou R. Role of hydrogen sulphide in airways. World J Respirol. Jul 28, 2015; 5(2): 152-159. https://www.wjgnet.com/2218-6255/full/v5/i2/152.htmtent block. Click the edit button to edit this text.