Ordonez Alvaro A, Bullen C Korin, Villabona-Rueda Andres F, Thompson Elizabeth A, Turner Mitchell L, Davis Stephanie L, Komm Oliver, Powell Jonathan D, D'Alessio Franco R, Yolken Robert H, Jain Sanjay K, Jones-Brando Lorraine
bioRxiv. 2021 Mar 25:2021.03.25.437060. doi: 10.1101/2021.03.25.437060.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection or treatment of early disease.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是2019冠状病毒病(COVID-19)的病原体,引发了一场全球健康危机。目前,对于接触SARS-CoV-2的人群,尚无口服预防药物;对于感染COVID-19的患者,治疗选择也有限。我们评估了萝卜硫素(SFN)的抗病毒活性,它是一种天然存在、口服可用、耐受性良好的营养补充剂,在十字花科蔬菜中含量很高,副作用有限。SFN在体外抑制了四株SARS-CoV-2以及季节性冠状病毒HCoV-OC43的复制。此外,SFN和瑞德西韦在体外协同作用抑制冠状病毒感染。在经鼻感染SARS-CoV-2之前,对K18-hACE2小鼠预防性给予SFN,与未治疗的感染小鼠相比,显著降低了肺部和上呼吸道的病毒载量,并减轻了肺损伤和肺部病理变化。SFN治疗减少了肺部免疫细胞的激活,包括显著降低髓样细胞的募集以及减少T细胞激活和细胞因子产生。我们的结果表明,SFN是预防冠状病毒感染或治疗早期疾病的一种有前景的治疗方法。