Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Microbiology and System Biology, Netherlands Organisation for Applied Scientific Research, Zeist, the Netherlands.
Antioxid Redox Signal. 2021 Nov 10;35(14):1207-1225. doi: 10.1089/ars.2020.8247. Epub 2021 Mar 25.
Hydrogen sulfide (HS) 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 HS in this viral respiratory disease. HS 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 HS. Combining HS physiology and currently available knowledge of COVID-19, HS 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). Dissecting the breakdown of NAC reveals the possibility of increasing endogenous HS levels, which may provide a convenient rationale for the application of HS-targeted therapeutics. Further randomized-controlled trials are warranted to investigate its definitive role.
硫化氢（HS）是人体中内源性产生的三种主要气体递质之一，可抵抗氧化应激。最近对由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）的研究结果引起了人们的关注，这些研究结果表明 HS 在这种病毒性呼吸道疾病中可能具有调节作用。入院时的 HS 水平可能很重要，因为这种气体递质已被证明通过其抗病毒、抗氧化和抗炎作用来保护肺免受损伤。此外，已经描述了许多 COVID-19 病例，在给予大剂量 N-乙酰半胱氨酸（NAC）后，这些病例显示出显著的临床改善。NAC 是一种著名的药理学抗氧化物质，可作为半胱氨酸的来源，从而促进内源性谷胱甘肽（GSH）的生物合成，并在脱硫为 HS 时生成硫烷硫物种。结合 HS 生理学和目前对 COVID-19 的了解，HS 被假设针对 SARS-CoV-2 的三个主要弱点：（i）通过干扰功能性宿主受体进入细胞，（ii）通过作用于 RNA 依赖性 RNA 聚合酶（RdRp）进行病毒复制，以及（iii）将炎症升级为潜在致命的过度炎症细胞因子风暴（ toll 样受体 4 [TLR4]途径和富含半胱氨酸的亮氨酸丰富重复蛋白 3 [NLRP3]炎性小体）。剖析 NAC 的分解揭示了增加内源性 HS 水平的可能性，这可能为应用 HS 靶向治疗提供便利的依据。需要进一步的随机对照试验来研究其明确作用。
