Abstract
Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has been widely spread in the world with a high mortality. Cytokine storm syndrome (CSS) and acute lung injury caused by SARS-CoV-2 infection severely threaten the patients. With the purpose to find effective and low-toxic drugs to mitigate CSS, entecavir and imipenem were identified to reduce TNF-α using a LPS-induced macrophage model from the anti-infective drug library. Entecavir and imipenem efficiently suppressed the release of inflammatory cytokines by partly intervention of NF-κB activity. The acute lung injury was also alleviated and the survival time was prolonged in mice. In addition, entecavir and imipenem inhibited the release of TNF-α and IL-10 in human peripheral blood mononuclear cells (hPBMCs). Collectively, we proposed that entecavir and imipenem might be candidates for the treatment of CSS.
【저자키워드】 Coronavirus disease 2019, acute respiratory distress syndrome, Cytokine storm syndrome, interleukin, Bronchoalveolar lavage fluid, lipopolysaccharide, Middle East respiratory syndrome, COVID-19coronavirus disease 2019, ARDSacute respiratory distress syndrome, ILInterleukin, MERSMiddle East Respiratory Syndrome, LPSlipopolysaccharide, BALFbronchoalveolar lavage fluid, CSScytokine storm syndrome, CCL-5chemokine (C-C motif) ligand 5, chemokine (C-C motif) ligand 5, CXCL1CXC chemokine ligand 1, CXC chemokine ligand 1, FDAU.S. Food and Drug Administration, U.S. Food and Drug Administration, G-CSFgranulocyte-colony stimulating factor, granulocyte-colony stimulating factor, hPBMChuman peripheral blood mononuclear cell, human peripheral blood mononuclear cell, IC50half-maximal inhibitory concentration, half-maximal inhibitory concentration, IP10interferon-γ-inducible protein 10, interferon-γ-inducible protein 10, MCP-1monocyte chemoattractant protein -1, monocyte chemoattractant protein -1, MIP-1αmacrophage inflammatory protein 1 alpha, macrophage inflammatory protein 1 alpha, NLRP3NLR family PYRIN domain containing-3, NLR family PYRIN domain containing-3, SARS-CoV-2Severe Acute Respiratory Syndrome Coronavirus -2, Severe Acute Respiratory Syndrome Coronavirus -2, 【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Macrophage, SARS-COV-2 infection, Intervention, drug, acute lung injury, Peripheral blood, Spread, survival, mice, IL-10, respiratory, patients, Inflammatory cytokine, TNF-α, NF-κB, mononuclear cell, entecavir, syndrome, high mortality, candidate, drug library, mitigate, effective, caused, addition, inhibited, suppressed, reduce, CSS, 【제목키워드】 Drug repurposing, anti-cytokine storm,