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

被引：78

作者：

Wang, Gan ^{[1
,2
]}

Yang, Meng-Li ^{[3
]}

Duan, Zi-Lei ^{[1
,2
]}

Liu, Feng-Liang ^{[1
,2
]}

Jin, Lin ^{[1
,2
]}

Long, Cheng-Bo ^{[1
,2
]}

Zhang, Min ^{[1
,2
,4
]}

Tang, Xiao-Peng ^{[1
,2
,5
]}

Xu, Ling ^{[1
,2
]}

Li, Ying-Chang ^{[1
,2
]}

Kamau, Peter Muiruri ^{[1
,2
,4
,5
]}

Yang, Lian ^{[6
]}

Liu, Hong-Qi ^{[3
]}

Xu, Jing-Wen ^{[3
]}

Chen, Jie-Kai ^{[7
]}

Zheng, Yong-Tang ^{[1
,2
,8
]}

Peng, Xiao-Zhong ^{[3
]}

Lai, Ren ^{[1
,2
,5
,8
,9
]}

机构：

[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

来源：

CELL RESEARCH | 2021年 / 31卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SARS; ENTRY; MERS;

D O I：

10.1038/s41422-020-00450-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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.

引用

页码：17 / 24

页数：8