Translational Research Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, 00149 Rome, Italy.
Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Cells. 2021 Dec 24;11(1):52. doi: 10.3390/cells11010052.
The ongoing pandemic of coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), needs better treatment options both at antiviral and anti-inflammatory levels. It has been demonstrated that the aminothiol cysteamine, an already human applied drug, and its disulfide product of oxidation, cystamine, have anti-infective properties targeting viruses, bacteria, and parasites. To determine whether these compounds exert antiviral effects against SARS-CoV-2, we used different in vitro viral infected cell-based assays. Moreover, since cysteamine has also immune-modulatory activity, we investigated its ability to modulate SARS-CoV-2-specific immune response in vitro in blood samples from COVID-19 patients. We found that cysteamine and cystamine decreased SARS-CoV-2-induced cytopathic effects (CPE) in Vero E6 cells. Interestingly, the antiviral action was independent of the treatment time respect to SARS-CoV-2 infection. Moreover, cysteamine and cystamine significantly decreased viral production in Vero E6 and Calu-3 cells. Finally, cysteamine and cystamine have an anti-inflammatory effect, as they significantly decrease the SARS-CoV-2 specific IFN-γ production in vitro in blood samples from COVID-19 patients. Overall, our findings suggest that cysteamine and cystamine exert direct antiviral actions against SARS-CoV-2 and have in vitro immunomodulatory effects, thus providing a rational to test these compounds as a novel therapy for COVID-19.
由严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)大流行仍需要更好的治疗选择,包括抗病毒和抗炎两个层面。已有研究表明,氨硫醇半胱氨酸,一种已应用于人类的药物,及其氧化二硫化物胱胺,具有针对病毒、细菌和寄生虫的抗感染特性。为了确定这些化合物是否对 SARS-CoV-2 具有抗病毒作用,我们使用了不同的基于感染细胞的体外病毒检测方法。此外,由于半胱氨酸还具有免疫调节活性,我们还研究了其在 COVID-19 患者血液样本中调节 SARS-CoV-2 特异性免疫反应的能力。我们发现半胱氨酸和胱胺可降低 SARS-CoV-2 在 Vero E6 细胞中引起的细胞病变效应(CPE)。有趣的是,这种抗病毒作用与 SARS-CoV-2 感染后治疗时间无关。此外,半胱氨酸和胱胺可显著降低 Vero E6 和 Calu-3 细胞中的病毒产量。最后,半胱氨酸和胱胺具有抗炎作用,因为它们可显著降低 COVID-19 患者血液样本中 SARS-CoV-2 特异性 IFN-γ的体外产生。总之,我们的研究结果表明,半胱氨酸和胱胺对 SARS-CoV-2 具有直接的抗病毒作用,并具有体外免疫调节作用,为测试这些化合物作为 COVID-19 的新型治疗方法提供了依据。