Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients
Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients
复制标题
DOI：
10.3390/jcm9061770
复制
发表时间：
2020-06-01
影响因子：
3.9
通讯作者：
Menendez, Javier A.
中科院分区：
文献类型：
--
作者：
Bosch-Barrera, Joaquim;Martin-Castillo, Begona;Menendez, Javier A.
COVID-19 是由新型冠状病毒 SARS-CoV-2 感染引起的疾病，是一种迅速蔓延的全球流行病，迫切需要有效的治疗。在这里，我们对黄酮木脂素水飞蓟宾的宿主和病毒靶向功能进行了全面检查，黄酮木脂素水飞蓟宾是一种针对 COVID-19/SARS-CoV-2 的潜在候选药物。作为炎症细胞因子信号传导和免疫反应的主要检查点调节剂 STAT3 的直接抑制剂，水飞蓟宾可能有望在表型上整合 IL-6 靶向单克隆抗体和泛 JAK1/2 抑制剂的作用机制，以限制严重 COVID-19 临床环境中的细胞因子风暴和 T 细胞淋巴细胞减少。正如计算预测的那样，RNA 依赖性 RNA 聚合酶 (RdRp) 的瑞德西韦样抑制剂（RdRp 是 SARS-CoV-2 复制/转录机制的核心成分）-水飞蓟宾有望减少病毒载量并阻止延迟的干扰素反应。水飞蓟宾针对宿主细胞因子风暴和病毒复制机制的双重能力为水飞蓟宾针对 COVID-19 全球公共卫生紧急情况的临床测试提供了强有力的理由。一项随机、开放标签、II 期多中心临床试验 (SIL-COVID19) 将在西班牙加泰罗尼亚加泰罗尼亚肿瘤研究所评估水飞蓟宾预防中重度 COVID-19 阳性肿瘤血液病患者急性呼吸窘迫综合征的治疗效果。
COVID-19, the illness caused by infection with the novel coronavirus SARS-CoV-2, is a rapidly spreading global pandemic in urgent need of effective treatments. Here we present a comprehensive examination of the host- and virus-targeted functions of the flavonolignan silibinin, a potential drug candidate against COVID-19/SARS-CoV-2. As a direct inhibitor of STAT3-a master checkpoint regulator of inflammatory cytokine signaling and immune response-silibinin might be expected to phenotypically integrate the mechanisms of action of IL-6-targeted monoclonal antibodies and pan-JAK1/2 inhibitors to limit the cytokine storm and T-cell lymphopenia in the clinical setting of severe COVID-19. As a computationally predicted, remdesivir-like inhibitor of RNA-dependent RNA polymerase (RdRp)-the central component of the replication/transcription machinery of SARS-CoV-2-silibinin is expected to reduce viral load and impede delayed interferon responses. The dual ability of silibinin to target both the host cytokine storm and the virus replication machinery provides a strong rationale for the clinical testing of silibinin against the COVID-19 global public health emergency. A randomized, open-label, phase II multicentric clinical trial (SIL-COVID19) will evaluate the therapeutic efficacy of silibinin in the prevention of acute respiratory distress syndrome in moderate-to-severe COVID-19-positive onco-hematological patients at the Catalan Institute of Oncology in Catalonia, Spain.