Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients

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ID: 119405
2020
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Abstract
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.
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bosch-barrera2020journalsilibinin Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Joaquim Bosch-Barrera;Begoña Martin-Castillo;Maria Buxó;Joan Brunet;José Antonio Encinar;Javier A. Menendez;Bosch-Barrera, Joaquim;Martin-Castillo, Begoña;Buxó, Maria;Brunet, Joan;Encinar, José Antonio;Menendez, Javier A.;
Journal journal of clinical medicine
Year 2020
DOI
10.3390/jcm9061770
URL
https://www.mdpi.com/2077-0383/9/6/1770
Keywords
stat3 coronavirus senescence il-6 cytokine storm remdesivir jak

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