Print Email Facebook Twitter N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019 Title N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019 Author Bourgonje, A.R. Offringa, A.K. van Eijk, L.E. Abdulle, A.E. Hillebrands, J.L. van der Voort, P.H.J. van Goor, H. van Hezik, E.J. Publication year 2021 Abstract Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a potentially modulatory role of H2S in this viral respiratory disease. Recent Advances: H2S levels at hospital admission may be of importance since this gasotransmitter has been shown to be protective against lung damage through its antiviral, antioxidant, and anti-inflammatory actions. Furthermore, many COVID-19 cases have been described demonstrating remarkable clinical improvement upon administration of high doses of N-acetylcysteine (NAC). NAC is a renowned pharmacological antioxidant substance acting as a source of cysteine, thereby promoting endogenous glutathione (GSH) biosynthesis as well as generation of sulfane sulfur species when desulfurated to H2S. Critical Issues: Combining H2S physiology and currently available knowledge of COVID-19, H2S is hypothesized to target three main vulnerabilities of SARS-CoV-2: (i) cell entry through interfering with functional host receptors, (ii) viral replication through acting on RNA-dependent RNA polymerase (RdRp), and (iii) the escalation of inflammation to a potentially lethal hyperinflammatory cytokine storm (toll-like receptor 4 [TLR4] pathway and NLR family pyrin domain containing 3 [NLRP3] inflammasome). Future Directions: Dissecting the breakdown of NAC reveals the possibility of increasing endogenous H2S levels, which may provide a convenient rationale for the application of H2S-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role. © Copyright 2021, Mary Ann Liebert, Inc., publishers 2021. Chemicals / CAS acetylcysteine, 616-91-1; amino acid, 65072-01-7; coronavirus RNA dependent RNA polymerase; glutathione, 70-18-8; hydrogen sulfide, 15035-72-0, 7783-06-4; RNA directed RNA polymerase, 9026-28-2; taurine, 107-35-7; taurolidine, 19388-87-5; toll like receptor 4, 203811-83-0; Acetylcysteine; Hydrogen Sulfide. Subject COVID-19hydrogen sulfideN-acetylcysteinereactive sulfur speciestaurineacetylcysteineamino acidangiotensin converting enzyme 2antioxidantantivirus agentcryopyringasotransmitterglutathionehost factorhydrogen sulfideinflammasomereactive sulfur speciesRNA directed RNA polymerasesulfur derivativetaurinetaurolidinetoll like receptor 4acetylcysteinehydrogen sulfideantiinflammatory activityantioxidant activityantiviral activityblood levelcase reportcoronavirus disease 2019cytokine stormdrug megadoseglutathione metabolismhospital admissionhumaninflammationinnate immunitylung injurynebulizationoxidation reduction stateoxidative stresspathophysiologypharmacologyphysiologyprognosispyrin domainreactive species interactomeReviewSevere acute respiratory syndrome coronavirus 2treatment indicationvirus replicationmetabolismoxidation reduction reactionAcetylcysteineCOVID-19HumansHydrogen SulfideOxidation-Reduction To reference this document use: http://resolver.tudelft.nl/uuid:e5153ae5-7ded-492a-9380-ba60e90dda58 DOI https://doi.org/10.1089/ars.2020.8247 TNO identifier 967685 ISSN 1523-0864 Source Antioxidants and Redox Signaling, 35 (35), 1207-1225 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.