Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation  

作　　者：Wei Wang Sha-sha Li Xin-feng Xu Chan Yang Xiao-ge Niu Shu-xian Yin Xiao-yan Pan Wei Xu Guo-dong Hu Chan Wang Shu-wen Liu 

机构地区：[1]Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China [2]Department of Respiratory and Critical Care Medicine,Nanfang Hospital,Southern Medical University,Guangzhou,510515,China [3]State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071,China [4]State Key Laboratory of Organ Failure Research,Guangdong Provincial Institute of Nephrology,Southern Medical University,Guangzhou,510515,China

出　　处：《Acta Pharmacologica Sinica》2022年第4期771-780,共10页中国药理学报（英文版）

基　　金：These authors gratefully acknowledge financial support from the Major Scientific and Technological Projects of Guangdong Province(2019B020202002);Chinese Academy of Traditional Chinese Medicine(ZZ13-035-02,2019XZZX-LG04)to SWL;Guangzhou Science and Technology Program(202008040001,201803040006 to WX and 2020B111110001 to SWL);National Natural Science Foundation of China(82070083 to GDH).

摘　　要：Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can induce acute inflammatory response like acute lung inflammation(ALI)or acute respiratory distress syndrome,leading to severe progression and mortality.Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered.Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection.In this study,we investigated the antiviral effects of a Salvia miltiorrhiza compound,Danshensu,in vitro and in vivo,including the mechanism of S protein-mediated virus attachment and entry into target cells.In authentic and pseudo-typed virus assays in vitro,Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97μM,and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus(SARS-CoV-2 S)into ACE2-overexpressed HEK-293T cells(IC50=0.31μM)and Vero-E6 cell(IC50=4.97μM).Mice received SARS-CoV-2 S via trachea to induce ALI,while the VSV-G treated mice served as controls.The mice were administered Danshensu(25,50,100 mg/kg,i.v.,once)or Danshensu(25,50,100 mg·kg-1·d-1,oral administration,for 7 days)before SARS-CoV-2 S infection.We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration,severely damaged lung tissue structure,highly expressed levels of inflammatory cytokines,and activated TLR4 and hyperphosphorylation of the NF-κB p65;the high expression of angiotensinogen(AGT)and low expression of ACE2 at the mRNA level in the lung tissue were also observed.Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S.This study not only establishes a mouse model of pseudo-typed SARS-CoV-2(SARS-CoV-2 S)induced ALI,but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.

关 键 词：DANSHENSU SARS-CoV-2 spike protein acute lung inflammation inflammatory cytokines 

分 类 号：R73[医药卫生—肿瘤]