tetano
Editor, Senior Moderator
J Clin Med
. 2020 Jun 7;9(6):E1770.
doi: 10.3390/jcm9061770.
Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients
Joaquim Bosch-Barrera[SUP] 1 2 [/SUP], Bego?a Martin-Castillo[SUP] 3 [/SUP], Maria Bux?[SUP] 4 [/SUP], Joan Brunet[SUP] 1 5 [/SUP], Jos? Antonio Encinar[SUP] 6 [/SUP], Javier A Menendez[SUP] 4 7 [/SUP]
Affiliations
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.
Keywords: IL-6; JAK; coronavirus; cytokine storm; remdesivir; senescence; stat3.
. 2020 Jun 7;9(6):E1770.
doi: 10.3390/jcm9061770.
Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients
Joaquim Bosch-Barrera[SUP] 1 2 [/SUP], Bego?a Martin-Castillo[SUP] 3 [/SUP], Maria Bux?[SUP] 4 [/SUP], Joan Brunet[SUP] 1 5 [/SUP], Jos? Antonio Encinar[SUP] 6 [/SUP], Javier A Menendez[SUP] 4 7 [/SUP]
Affiliations
- PMID: 32517353
- DOI: 10.3390/jcm9061770
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.
Keywords: IL-6; JAK; coronavirus; cytokine storm; remdesivir; senescence; stat3.