Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, Guangdong Pharmaceutical University, Guangzhou 510080, China.
Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
Int J Mol Sci. 2020 Sep 29;21(19):7189. doi: 10.3390/ijms21197189.
The world is currently experiencing the worst health pandemic since the Spanish flu in 1918-the COVID-19 pandemic-caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the world's third wake-up call this century. In 2003 and 2012, the world experienced two major coronavirus outbreaks, SARS-CoV-1 and Middle East Respiratory syndrome coronavirus (MERS-CoV), causing major respiratory tract infections. At present, there is neither a vaccine nor a cure for COVID-19. The severe COVID-19 symptoms of hyperinflammation, catastrophic damage to the vascular endothelium, thrombotic complications, septic shock, brain damage, acute disseminated encephalomyelitis (ADEM), and acute neurological and psychiatric complications are unprecedented. Many COVID-19 deaths result from the aftermath of hyperinflammatory complications, also referred to as the "cytokine storm syndrome", endotheliitus and blood clotting, all with the potential to cause multiorgan dysfunction. The sphingolipid rheostat plays integral roles in viral replication, activation/modulation of the immune response, and importantly in maintaining vasculature integrity, with sphingosine 1 phosphate (S1P) and its cognate receptors (SIPRs: G-protein-coupled receptors) being key factors in vascular protection against endotheliitus. Hence, modulation of sphingosine kinase (SphK), S1P, and the S1P receptor pathway may provide significant beneficial effects towards counteracting the life-threatening, acute, and chronic complications associated with SARS-CoV-2 infection. This review provides a comprehensive overview of SARS-CoV-2 infection and disease, prospective vaccines, and current treatments. We then discuss the evidence supporting the targeting of SphK/S1P and S1P receptors in the repertoire of COVID-19 therapies to control viral replication and alleviate the known and emerging acute and chronic symptoms of COVID-19. Three clinical trials using FDA-approved sphingolipid-based drugs being repurposed and evaluated to help in alleviating COVID-19 symptoms are discussed.
目前，世界正面临自 1918 年西班牙流感以来最严重的卫生大流行——由冠状病毒严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的 COVID-19 大流行。这场大流行是本世纪世界第三次敲响警钟。2003 年和 2012 年，世界经历了两次主要的冠状病毒爆发，即 SARS-CoV-1 和中东呼吸综合征冠状病毒（MERS-CoV），造成了严重的呼吸道感染。目前，COVID-19 既没有疫苗也没有治愈方法。COVID-19 的严重症状包括过度炎症、血管内皮的灾难性损伤、血栓并发症、感染性休克、脑损伤、急性播散性脑脊髓炎（ADEM）和急性神经和精神并发症等，这些都是前所未有的。许多 COVID-19 死亡是由过度炎症并发症引起的，也称为“细胞因子风暴综合征”、内皮炎症和血栓形成引起的，所有这些都有可能导致多器官功能障碍。鞘脂调节剂在病毒复制、免疫反应的激活/调节以及维持血管完整性方面发挥着重要作用，其中神经鞘氨醇 1 磷酸（S1P）及其同源受体（SIPR：G 蛋白偶联受体）是血管内皮炎症的关键保护因素。因此，鞘氨醇激酶（SphK）、S1P 和 S1P 受体途径的调节可能对对抗与 SARS-CoV-2 感染相关的危及生命的急性和慢性并发症具有显著的有益作用。本综述全面概述了 SARS-CoV-2 感染和疾病、有前途的疫苗和当前的治疗方法。然后，我们讨论了支持靶向 SphK/S1P 和 S1P 受体作为 COVID-19 治疗方案的证据，以控制病毒复制并缓解 COVID-19 的已知和新出现的急性和慢性症状。讨论了正在重新利用和评估三种使用 FDA 批准的鞘脂类药物的临床试验，以帮助缓解 COVID-19 症状。
