Herbal inhibitors of SARS-CoV-2 Mpro effectively ameliorate acute lung injury in mice

SARS-CoV-2 Mpro 的草药抑制剂可有效改善小鼠的急性肺损伤

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作者:Xinyi Du, Longxin Xu, Yiming Ma, Shuaiyao Lu, Kegong Tang, Xiangyu Qiao, Jiaqi Liu, Xiaona Wang, Xiaozhong Peng, Chengyu Jiang

Abstract

Coronavirus disease 2019, a newly emerging serious infectious disease, has spread worldwide. To date, effective drugs against the disease are limited. Traditional Chinese medicine was commonly used in treating COVID-19 patients in China. Here we tried to identify herbal effective lipid compounds from the lipid library of 92 heat-clearing and detoxication Chinese herbs. Through virtual screening, enzymatic activity and inhibition assays, and surface plasmon resonance tests, we identified lipid compounds targeting the main protease (Mpro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and verified their functions. Here, we found that natural lipid compounds LPC (14:0/0:0) and LPC (16:0/0:0) could target SARS-CoV-2 Mpro , recover cell death induced by SARS-CoV-2, and ameliorate acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by bacterial lipopolysaccharides and virus poly (I:C) mimics in vivo and in vitro. Our results suggest that LPC (14:0/0:0) and LPC (16:0/0:0) might be potential pan remedy against ARDS.

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