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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
Wang,Gan; Yang,Meng-Li; Duan,Zi-Lei; Liu,Feng-Liang; Jin,Lin; Long,Cheng-Bo; Zhang,Min; Tang,Xiao-Peng; Xu,Ling; Li,Ying-Chang; Kamau,Peter Muiruri; Yang,Lian; Liu,Hong-Qi; Xu,Jing-Wen; Chen,Jie-Kai; Zheng,Yong-Tang; Peng,Xiao-Zhong; Lai,Ren
2021
发表期刊CELL RESEARCH
ISSN1001-0602
卷号31期号:1页码:17-24
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 anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, 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 similar to 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SARS ENTRY MERS
DOI10.1038/s41422-020-00450-0
WOS记录号WOS:000595392700004
引用统计
被引频次:70[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/73006
专题中国科学院昆明植物研究所
作者单位1.Chinese Acad Sci, Kunming Primate Res Ctr, Key Lab Anim Models & Human Dis Mech,Natl Resourc, Key Lab Bioact Peptides Yunnan Prov,KIZ CUHK Join, Kunming 650107, Yunnan, Peoples R China
2.Kunming Inst Zool, Natl Res Facil Phenotyp & Genet Anal Model Anim P, Kunming 650107, Yunnan, Peoples R China
3.Chinese Acad Med Sci, Peking Union Med Coll, Inst Med Biol, Kunming 650031, Yunnan, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Sino African Joint Res Ctr, Wuhan 430074, Hubei, Peoples R China
6.Chinese Acad Sci, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China
7.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China
8.Chinese Acad Sci, Ctr Biosafety Megasci, Kunming Natl High Level Biosafety Res Ctr Nonhuma, Kunming Inst Zool, Kunming 650107, Yunnan, Peoples R China
9.Chinese Acad Sci, Inst Drug Discovery & Dev, Shanghai 201203, Peoples R China
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Wang,Gan,Yang,Meng-Li,Duan,Zi-Lei,et al. 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[J]. CELL RESEARCH,2021,31(1):17-24.
APA Wang,Gan.,Yang,Meng-Li.,Duan,Zi-Lei.,Liu,Feng-Liang.,Jin,Lin.,...&Lai,Ren.(2021).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.CELL RESEARCH,31(1),17-24.
MLA Wang,Gan,et al."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".CELL RESEARCH 31.1(2021):17-24.
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