Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation
作者单位：Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical University Department of Respiratory and Critical Care MedicineNanfang HospitalSouthern Medical University State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of Sciences State Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologySouthern Medical University
会议名称：《2022第27届广东省药师周大会》
会议日期：2021年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：Danshensu SARS-CoV-2 Spike acute lung inflammation inflammatory cytokines
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 *** for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be *** previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 *** 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 *** authentic and pseudo-typed virus assays in vitro,Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 μM,and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus(SARS-Co V-2 S) into ACE2-overexpressed HEK-293 T cells(IC50 = 0.31 μM) and Vero-E6 cell(IC50 = 4.97 μM).Mice received SARS-CoV-2 S via trachea to induce ALI,while the VSV-G treated mice served as *** 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 *** 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 *** oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 *** 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.