Ceftazidime Is a Potential Drug to Inhibit SARS-CoV-2 Infection In Vitro by Blocking Spike Protein-ACE2 Interaction
作者单位：State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of Sciences State Key Laboratory of Molecular BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of Sciences School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences
会议名称：《中国生物化学与分子生物学会2020全国学术在线会议》
会议日期：2020年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：Ceftazidime SARS-CoV-2 S-RBD ACE2 COVID-19
摘 要：Coronavirus Disease 2019(COVID-19) spreads globally as a sever pandemic,which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Cell entry of SARS-CoV-2 mainly depends on binding of the viral spike(S) proteins to angiotensin converting enzyme 2(ACE2) on host ***,repurposing of known drugs to inhibit S protein-ACE2 interaction could be a quick way to develop effective therapy for *** a high-throughput screening system to investigate the interaction between spike receptor binding domain(S-RBD) and ACE2 extracellular domain,we screened3581 FDA-approved drugs and natural small molecules and identified ceftazidime as a potent compound to inhibit S-RBDACE2 interaction by binding to *** addition to significantly inhibit S-RBD binding to HPAEpiC cells,ceftazidime efficiently prevented SARS-CoV-2 pseudovirus to infect ACE2-expressing 293 T *** inhibitory concentration(IC50)was 113.2 μM,which is far below the blood concentration(over 300 μM) of ceftazidime in patients when clinically treated with recommended ***,ceftazidime is a drug clinically used for the treatment of pneumonia with minimal side effects compared with other antiviral ***,ceftazidime has both anti-bacterial and anti-SARS-CoV-2 effects,which should be the first-line antibiotics used for the clinical treatment of COVID-19.