Volume 31, No 1, Jan 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 1, January 2021: 17-24   |  Open Access

ORIGINAL ARTICLES

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

Gan Wang¹ , Meng-Li Yang² , Zi-Lei Duan¹ , Feng-Liang Liu¹ , Lin Jin¹ , Cheng-Bo Long¹ , Min Zhang^1,3 , Xiao-Peng Tang^1,4 , Ling Xu¹ , Ying-Chang Li¹ , Peter Muiruri Kamau^1,3,4 , Lian Yang⁵ , Hong-Qi Liu² , Jing-Wen Xu² , Jie-Kai Chen⁶ , Yong-Tang Zheng^1,7,* , Xiao-Zhong Peng^2,* , Ren Lai^1,4,7,8,*

¹Key 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
²Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, Yunnan 650031, China
³University of Chinese Academy of Sciences, Beijing 100049, China
⁴Sino-African Joint Research Center, Chinese Academy of Science, Wuhan, Hubei 430074, China
⁵Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China
⁶Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China
⁷Kunming 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
⁸Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai 201203, China
These authors contributed equally: Gan Wang, Meng-Li Yang, Zi-Lei Duan, Feng-Liang Liu, Lin Jin Correspondence: Yong-Tang Zheng(zhengyt@mail.kiz.ac.cn)Xiao-Zhong Peng(pengxiaozhong@pumc.edu.cn)Ren Lai(rlai@mail.kiz.ac.cn)

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 ~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.

https://doi.org/10.1038/s41422-020-00450-0

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