Batiha Gaber El-Saber, Al-Gareeb Ali I, Rotimi Damilare, Adeyemi Oluyomi Stephen, Al-Kuraishy Hayder M
Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, AlBeheira, Damanhour 22511, Egypt.
Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq.
Sci Afr. 2022 Nov;18:e01407. doi: 10.1016/j.sciaf.2022.e01407. Epub 2022 Oct 22.
Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon-gamma (INF-γ), while inhibiting IL-33 expression. Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm-induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.
严重的新型冠状病毒2型（SARS-CoV-2）感染会引发全身炎症、细胞因子风暴和高细胞因子血症，这是由于促炎细胞因子的释放被激活，而这些促炎细胞因子与病死率相关。SARS-CoV-2感染中免疫反应过度和细胞因子风暴可能与NLRP3炎性小体激活有关，NLRP3炎性小体激活在主要针对病毒感染的人类固有免疫反应中至关重要。在SARS-CoV-2感染中，NLRP3炎性小体激活会刺激和合成自然杀伤细胞（NKs）、核因子κB（NFκB）和干扰素-γ（INF-γ），同时抑制白细胞介素-33（IL-33）的表达。多项研究已鉴定出NLRP3炎性小体的选择性抑制剂。为实现这一目标，研究正在探索筛选天然化合物和/或重新利用临床药物以确定潜在的NLRP3抑制剂。NLRP3炎性小体抑制剂有望抑制SARS-CoV-2感染中过度的免疫反应和细胞因子风暴诱导的器官损伤。因此，NLRP3炎性小体抑制剂可以减轻新型冠状病毒病（Covid-19）感染中的免疫反应过度和高细胞因子血症。
