The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy

Lin, Hongyuan

doi:10.1016/j.cjtee.2020.06.002

Cited by 39 publications

(40 citation statements)

References 64 publications

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“…Sepsis is a systemic inflammatory response elicited by microbial infection and the leading cause of mortality in critically ill patients ( 9 ). The ultimate cause of death in sepsis is mostly attributed to the multiple organ dysfunction syndrome (MODS) due to uncontrolled inflammatory response to infection or injury, and the commonest sites of infection are the lungs, the liver, kidneys and intestinal tract ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

Jiang

Zhou

et al. 2021

Front. Immunol.

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CREB binding protein (CBP), a transcriptional coactivator and acetyltransferase, is involved in the pathogenesis of inflammation-related diseases. High mobility group box-1 protein (HMGB1) is a critical mediator of lethal sepsis, which has prompted investigation for the development of new treatment for inflammation. Here, we report that the potent and selective inhibition of CBP bromodomain by SGC-CBP30 blocks HMGB1-mediated inflammatory responses in vitro and in vivo. Our data suggest that CBP bromodomain inhibition suppresses LPS-induced expression and release of HMGB1, when the inhibitor was given 8 h post LPS stimulation; moreover, CBP bromodomain inhibition attenuated pro-inflammatory activity of HMGB1. Furthermore, our findings provide evidence that SGC-CBP30 down-regulated rhHMGB1-induced activation of MAPKs and NF-κB signaling by triggering the reactivation of protein phosphatase 2A (PP2A) and the stabilization of MAPK phosphatase 1 (MKP-1). Collectively, these results suggest that CBP bromodomain could serve as a candidate therapeutic target for the treatment of lethal sepsis via inhibiting LPS-induced expression and release of HMGB1 and suppressing the pro-inflammatory activity of HMGB1.

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Section: Introductionmentioning

confidence: 99%

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

Jiang

Zhou

et al. 2021

Front. Immunol.

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“…Finally, with the outbreak of the COVID-19 pandemic, Tα1 recently gained new attention in virology. Clinical symptoms of COVID-19 to some extent resemble a pathogen-induced sepsis, which justifies immunomodulatory Tα1 treatment [ 21 ]. Along these lines, Chinese medical staff members at high risk of COVID-19 infection already received a weekly Tα1 injection in combination with human interferon 1 (hIFN-α) nasal drops as a prophylactic measure [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology

Binder¹,

Skerra

2020

IJMS

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Thymosin α1 (Tα1) is an immunostimulatory peptide for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and used as an immune enhancer, which also offers prospects in the context of COVID-19 infections and cancer. Manufacturing of this N-terminally acetylated 28-residue peptide is demanding, and its short plasma half-life limits in vivo efficacy and requires frequent dosing. Here, we combined the PASylation technology with enzymatic in situ N-acetylation by RimJ to produce a long-acting version of Tα1 in Escherichia coli at high yield. ESI-MS analysis of the purified fusion protein indicated the expected composition without any signs of proteolysis. SEC analysis revealed a 10-fold expanded hydrodynamic volume resulting from the fusion with a conformationally disordered Pro/Ala/Ser (PAS) polypeptide of 600 residues. This size effect led to a plasma half-life in rats extended by more than a factor 8 compared to the original synthetic peptide due to retarded kidney filtration. Our study provides the basis for therapeutic development of a next generation thymosin α1 with prolonged circulation. Generally, the strategy of producing an N-terminally protected PASylated peptide solves three major problems of peptide drugs: (i) instability in the expression host, (ii) rapid degradation by serum exopeptidases, and (iii) low bioactivity because of fast renal clearance.

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“…Overproduction of cytokines results in sepsis (Rittirsch et al 2008 ; Boomer et al 2011 ). Sepsis-induced organ dysfunction in COVID-19 patients has been reported (Lin 2020 ). Blood being the primary carrier for cytokine distribution to various tissues in the body, hemoperfusion has been suggested for severe sepsis/lung injury as reviewed (Chaudhry et al 2013 ; Schädler et al 2013 ).…”

Section: Potential Inhibitors Of Cytokine Storm In the Context Of Sarmentioning

confidence: 99%

Cancer vs. SARS-CoV-2 induced inflammation, overlapping functions, and pharmacological targeting

Subbarao

2021

Inflammopharmacol

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Inflammation is an intrinsic defence mechanism triggered by the immune system against infection or injury. Chronic inflammation allows the host to recover or adapt through cellular and humoral responses, whereas acute inflammation leads to cytokine storms resulting in tissue damage. In this review, we present the overlapping outcomes of cancer inflammation with virus-induced inflammation. The study emphasises how anti-inflammatory drugs that work against cancer inflammation may work against the inflammation caused by the viral infection. It is established that the cytokine storm induced in response to SARS-CoV-2 infection contributes to disease-associated mortality. While cancer remains the second among the diseases associated with mortality worldwide, cancer patients' mortality rates are often observed upon extended periods after illness, usually ranging from months to years. However, the mortality rates associated with COVID-19 disease are robust. The cytokine storm induced by SARS-CoV-2 infection appeared to be responsible for the multi-organ failure and increased mortality rates. Since both cancer and COVID-19 disease share overlapping inflammatory mechanisms, repurposing some anticancer and anti-inflammatory drugs for COVID-19 may lower mortality rates. Here, we review some of these inflammatory mechanisms and propose some potential chemotherapeutic agents to intervene in them. We also discuss the repercussions of anti-inflammatory drugs such as glucocorticoids and hydroxychloroquine with zinc or antiviral drugs such as ivermectin and remdesivir against SARS-CoV-2 induced cytokine storm. In this review, we emphasise on various possibilities to reduce SARS-CoV-2 induced cytokine storm.

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The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy

Cited by 39 publications

References 64 publications

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology

Cancer vs. SARS-CoV-2 induced inflammation, overlapping functions, and pharmacological targeting

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