Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models  

作　　者：Gan Wang Meng-Li Yang Zi-Lei Duan Feng-Liang Liu Lin Jin Cheng-Bo Long Min Zhang Xiao-Peng Tang Ling Xu Ying-Chang Li Peter Muiruri Kamau Lian Yang Hong-Qi Liu Jing-Wen Xu Jie-Kai Chen Yong-Tang Zheng Xiao-Zhong Peng Ren Lai 

机构地区：[1]Key Laboratory of Animal Models and Human Disease Mechanisms,Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province,KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,National Resource Center for Non-Human Primates,Kunming Primate Research Center,and National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility),Kunming Institute of Zoology,Kunming,Yunnan 650107,China [2]Institute of Medical Biology,Chinese Academy of Medical Sciences,Peking Union Medical College,Kunming,Yunnan 650031,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]Sino-African Joint Research Center,Chinese Academy of Science,Wuhan,Hubei 430074,China [5]Kunming Institute of Botany,Chinese Academy of Sciences,Kunming,Yunnan 650201,China [6]Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,Guangdong 510530,China [7]Kunming National High-level Biosafety Research Center for Non-human Primates,Center for Biosafety Mega-Science,Kunming Institute of Zoology Chinese Academic of Sciences,Kunming,Yunnan 650107,China [8]Institutes for Drug Discovery and Development,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Cell Research》2021年第1期17-24,共8页细胞研究（英文版）

基　　金：supported by fundings from the National Natural Science Foundation of China(81903666,21761142002,31600721,and 31930015);Chinese Academy of Sciences(SAJC201606 and ZSTH-034);the National Key Research and Development Program of China(2020YFC0842000);Science and Technology Department of Yunnan Province(2019ZF003 and 2019FB103);Department of Industry and Information Technology of Yunnan Province(2019-YT-053).

摘　　要：Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a pandemic worldwide.Currently,however,no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019(COVID-19).Here,we report our discovery of a promising an ti-COVID-19 drug can didate,the lipoglycopeptide antibiotic dalbava ncin,based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays.Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2(ACE2)with high affinity,thereby blocking its interaction with the SARS-CoV-2 spike protein.Furthermore,dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC50 of~12 nM.In both mouse and rhesus macaque models,viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration.Given its high safety and long plasma half-life(8-10 days)shown in previous clinical trials,our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.

关 键 词：ACE2 injuries INFECTION 

分 类 号：R563.1[医药卫生—呼吸系统]