Drug repurposing of anti-infective clinical drugs: Discovery of two potential anti-cytokine storm agents

抗感染临床药物的再利用:发现两种潜在的抗细胞因子风暴药物

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作者:Li Su ,Ye Tu ,De-Pei Kong ,Da-Gui Chen ,Chen-Xi Zhang ,Wan-Nian Zhang ,Chun-Lin Zhuang ,Zhi-Bin Wang

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.

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